IndraLab

Statements


USP8 is modified
27 | 1 144 14
USP8 is phosphorylated.
27 | 120 14
USP8 is phosphorylated. 10 / 98
| 96 2

sparser
"Furthermore, we demonstrate that optimal Usp8 tyrosine phosphorylation is not necessary for binding of Usp8 to EGFR."

sparser
"The binding of BAP-treated UBPY to 14-3-3ε was significantly reduced compared to that of untreated UBPY, indicating that the phosphorylation of UBPY is required for its 14-3-3 binding ( Fig. 2 C)."

sparser
"The [ 32 P] labeling experiment also suggested the presence of other phosphorylation site(s) in UBPY because the phosphorylation of UBPY S680A was still faintly detected."

sparser
"To investigate how Usp8 tyrosine phosphorylation is regulated, we tested whether TGFα stimulation of EGFR leads to efficient Usp8 tyrosine phosphorylation."

sparser
"We therefore tested whether enhanced recycling of EGFR in response to TGFα stimulation leads to efficient Usp8 tyrosine phosphorylation."

sparser
"Our data support the model whereby EGF stimulation of the EGFR leads to MIT-domain dependent recruitment of Usp8 towards the activated receptor-complex at the endosomes where also the SRC kinases are [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"To test whether Src-family tyrosine kinases may be responsible for Usp8 tyrosine phosphorylation upon stimulation of EGFR-ErbB2, we used the specific Src-family kinase inhibitors PP2 and Src Inhibitor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"However, removal of the MIT domain did not completely abolish Usp8 tyrosine phosphorylation."

sparser
"Interestingly, overexpression of constitutively active mutant SRC (SRC Y527A) significantly increases USP8 tyrosine phosphorylation ."

sparser
"Moreover, co-expression of constitutively active SRC Y527A with EGFR and either Usp8 WT or C748A substantially increased basal and ligand-induced Usp8 tyrosine phosphorylation ( Fig. 2 A–B)."
USP8 is phosphorylated on tyrosine. 10 / 15
| 7 8

rlimsp
"Here, we demonstrate, in the context of a chimeric EGFR-ErbB2 receptor, that (i) EGF induces pY1091 Cbl binding site-dependent K63-polyubiquitination of EGFR-ErbB2, (ii) Cbl is tyrosine phosphorylated upon stimulation of EGFR-ErbB2 wt and Y1091F mutant receptor, (iii) EGF-induced activation of EGFR-ErbB2 induces Usp8 tyrosine phosphorylation, and (iv) ubiquitination of the EGFR-ErbB2 wt and Y1091F mutant is enhanced upon coexpression of catalytically inactive Usp8-C748A in the presence and absence of EGF."

rlimsp
"We also show that enhanced endosomal recycling of the EGFR induced by TGFα stimulation is associated with decreased Usp8 tyrosine phosphorylation."

rlimsp
"In the present study we show that overexpression of constitutively active SRC enhances constitutive and ligand-induced Usp8 tyrosine phosphorylation."

rlimsp
"However, mutation of three MIT domain tyrosine residues did not abolish Usp8 tyrosine phosphorylation."

rlimsp
"Our findings are most consistent with the model that MIT domain-dependent recruitment of Usp8 to endosomal membranes is important for low stoichiometry SRC-mediated tyrosine phosphorylation of multiple Usp8 tyrosines."

sparser
"However, since the tyrosine phosphorylation in the 1–504 construct was decreased compared to Usp8 WT, it is likely that more than a single tyrosine residue of Usp8 is phosphorylated."

sparser
"To identify the Usp8 tyrosine residues that are phosphorylated upon EGF-stimulation of EGFR, we first addressed the question which part of Usp8 is essential for binding to the EGFR and for subsequent [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

rlimsp
"We previously demonstrated that Usp8 is tyrosine phosphorylated in an EGFR- and SRC-kinase dependent manner."

sparser
"In contrast, TCHP is deubiquitinated by USP8 after EGFR-mediated phosphorylation of USP8 at tyrosine residues 717 and 810 [ xref ]."
| PMC

sparser
"Using Usp8 deletion constructs, our results demonstrate that Usp8 is efficiently tyrosine phosphorylated on at least one tyrosine residue in the N-terminal 504 amino acids of Usp8, as detected by immu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 is phosphorylated on S718. 10 / 15
7 | 6 2

sparser
"We therefore examined whether UBPY undergoes phosphorylation at Ser 680 ."

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sparser
"As with Usp8 phosphorylation of S680, serine phosphorylation of USP16 and USP44 plays a role during mitosis [35,63,64] ."

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sparser
"This phosphorylation of USP8 at S680 permits complex formation with 14-3-3 proteins ."

rlimsp
"Metabolic labeling with [(32)P]orthophosphate and immunoblotting using antibody against the phosphorylated 14-3-3-binding motif showed that Ser(680) is a major phosphorylation site in UBPY."

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sparser
"In the interphase stage of cell division, the Ser680 residue of USP8 is phosphorylated, which enables USP8 to bind to the 14-3-3 protein This binding in turn inhibits the catalytic activity of USP8 ( xref ) ( xref )."
USP8 is phosphorylated on Y717. 5 / 5
1 | 4

sparser
"Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells."

sparser
"USP8 phosphorylation on Tyr717 and Tyr810 by EGFR kinase elevates its activity and then activates an inhibitory mechanism of ciliogenesis, i.e., EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase [ xref ]."

sparser
"In contrast, Kasahara et al. [ xref ] reported that EGFR kinase suppresses ciliogenesis by phosphorylating USP8 on Tyr717 and Tyr810 enhancing the deubiquitinase activity."

sparser
"In this study, we show that EGFR activation is responsible for this process by directly phosphorylating USP8 on Tyr-717 and Tyr-810."

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USP8 is phosphorylated on Y810. 5 / 5
| 4 1

sparser
"Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells."

sparser
"In this study, we show that EGFR activation is responsible for this process by directly phosphorylating USP8 on Tyr-717 and Tyr-810."

rlimsp
"Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells."

sparser
"In contrast, Kasahara et al. [ xref ] reported that EGFR kinase suppresses ciliogenesis by phosphorylating USP8 on Tyr717 and Tyr810 enhancing the deubiquitinase activity."

sparser
"USP8 phosphorylation on Tyr717 and Tyr810 by EGFR kinase elevates its activity and then activates an inhibitory mechanism of ciliogenesis, i.e., EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase [ xref ]."
USP8 is phosphorylated on S392. 4 / 4
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USP8 is phosphorylated on S716. 4 / 4
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USP8 is phosphorylated on S434. 3 / 3
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USP8 is phosphorylated on S452. 3 / 3
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USP8 is phosphorylated on S389. 2 / 2
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USP8 is phosphorylated on S108. 2 / 2
1 | 1

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sparser
"In a previous study, MS analysis was used to demonstrate that Usp8 is phosphorylated on serines 108, 153 and 680, depending on the tissue of origin [55] ."
USP8 is phosphorylated on serine. 2 / 2
| 1 1

rlimsp
"The phosphorylation of USP8 on the fourth serine (S718) of its 14-3-3 binding motif results in its binding with 14-3-3 proteins and catalytic inactivation. A structural study demonstrated that within the 14-3-3 binding motif, the amino acid preferences in each position are very similar, and the phosphorylation of serine at the fourth position is essential for its binding ability."

sparser
"Phosphorylation of USP8 at additional Ser and Tyr residues has been reported to regulate its function although the exact outcomes are not yet defined [ xref ]."
USP8 is phosphorylated on S719. 2 / 2
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USP8 is phosphorylated on Y679. 1 / 1
| 1

sparser
"Although we obtained no direct evidence for phosphorylation of Usp8 Y679 in the site-directed mutagenesis study ( Fig. 7 ) and the MS experiments ( Fig. 8 ), we addressed whether phosphorylation of Y6[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 is ubiquitinated.
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USP8 is ubiquitinated. 10 / 15
| 15

sparser
"These data suggest a reciprocal E3-DUB relationship in which GRAIL can ubiquitinate USP8, and ubiquitinated USP8 can de-ubiquitinate GRAIL."

sparser
"In the present study the linkage between PTEN loss, Akt activation, and USP8 levels and activity appeared to be somewhat different, and in our work Akt activation decreased, rather than enhanced, USP8 function by increasing USP8 ubiquitination and decreasing steady-state USP8 levels (data not shown)."

sparser
"It does so by ubiquitinating, destabilizing and relocalizing the deubiquitinase USP8 (ubiquitin-specific protease 8)."

sparser
"In particular, IL-2R signaling leads to Akt and mTOR activation, Otub1 translation, de-ubiquitination of ubiquitinated USP8, and subsequent degradation of GRAIL that permits T cell proliferation."

sparser
"This effect is co-activated by the deubiquitinases USP8 and USP9X. The AKT kinase has been previously shown to decrease USP8 function by increasing USP8 ubiquitination and decreasing active steady-state USP8 level [ xref ]."

sparser
"This increased ubiquitination was dependent on the E3 activity of GRAIL, as no enhanced ubiquitination of USP8 was observed in the presence of the H2N2 ligase defective mutant of GRAIL."

sparser
"Next to ubiquitinating BRUCE, Parkin and USP8 [ xref , xref , xref ], it is known to downregulate ErbB3 and ErbB4 receptors, as well as several type I cytokine receptors such as the IL-3, EPO, IL-6, LIF and LR [ xref , xref – xref ]."

sparser
"Thus, our current working model is that Otub 1 promotes GRAIL degradation by de-ubiquitination of ubiquitinated USP8, thereby diminishing USP8 activity ( xref )."

sparser
"RNF41 redistributes and ubiquitylates USP8, and reduces USP8 levels."

sparser
"Others suggest that USP8 counter-regulates EGF-induced ubiquitination of the ESCRT-III component CHMP1B, allowing it to assemble into a membrane-associated ESCRT-III polymer required for budding [ xref ]."
USP8 is dephosphorylated.
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USP8 is dephosphorylated. 5 / 5
| 5

sparser
"This phosphorylation-mediated regulation of USP8 is present during the interphase, while during the M phase USP8 is dephosphorylated [ xref ]."

sparser
"The activation of NMDARs induces Ca 2+ -dependent dephosphorylation of USP8 by a still unknown tyrosine phosphatase, thereby enhancing its catalytic activity (Scudder et al., xref )."

sparser
"Upon N-methyl- d-aspartic acid receptor (NMDAR) activation, USP8 is dephosphorylated and facilitates the recycling of internalized AMPARs xref ."

sparser
"Finally, UBPY was dephosphorylated at Ser(680) and dissociated from 14-3-3s in the M phase, resulting in enhanced activity of UBPY during cell division."

sparser
"We show that NMDAR activation causes the rapid dephosphorylation and activation of the deubiquitinating enzyme (DUB) USP8."
USP8 is dephosphorylated on S718. 4 / 4
| 4

sparser
"In the present study, we showed that in the M phase, UBPY is dephosphorylated at Ser 680 , dissociated from 14-3-3s, and catalytically activated ( Figs."

sparser
"During M-phase of the cell cycle, Usp8 is dephosphorylated at S680, resulting in dissociation from 14–3–3 and enhanced Usp8 function during cell division [35] ."

sparser
"Meanwhile, in the M phase, the dephosphorylation of USP8 at Ser680 can enhance its catalytic activity ( xref ; xref )."

sparser
"7 C and D suggested that UBPY is dephosphorylated at Ser 680 in the M phase."
USP8 is produced.
| 1
USP8 is produced. 1 / 1
| 1

reach
"USP8 upregulated YY1 protein level through deubiquitination and YY1 activated USP8 transcription, and USP8-YY1 feedback loop attenuated cognitive dysfunction in SAE mice, which could potentially serve as a novel theoretical foundation for the management of SAE."
USP8 affects EGFR
18 7 1 | 3 72 14
USP8 deubiquitinates EGFR.
18 1 | 2 17
USP8 deubiquitinates EGFR. 10 / 16
1 | 1 14

reach
"USP8 (also known as UBPY) deubiquitylates EGFR on early endosomes, rescuing EGFR from degradation 107, 108 ."

reach
"Before incorporation into MVBs, the EGFR is deubiquitinated by Usp8."

reach
"However, we can not fully exclude the other possibility that the UBPY S680A expression resulted in a reduction in the cellular Ub conjugating activity toward activated EGFR in some way.The fact that U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III."

reach
"Some studies showed that AMSH [31] and UBPY [32, 33] prevent EGFR down-regulation by deubiquitinating EGFR."

reach
"While AMSH is required for sorting of EGFR into MVEs and degradation in lysosomes XREF_BIBR, deubiquitination of EGFR by USP8 protects it from lysosomal degradation XREF_BIBR."

reach
"If USP8 deubiquitylates EGFR at the MVB, this facilitates EGFR 's progression toward degradation in the lysosome and, thus, aids receptor down-regulation."

trips
"Immunopurified UBPY deubiquitinated EGFR in vitro."

reach
"Gain-of-function mutations in USP8 increase the deubiquitination of EGFR, which inhibits its degradation, leading to the activation of EGFR signaling."
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, K929, Y1092, Y1016, Y1197, K970, and Y1069 on K716. 3 / 3
3 |

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USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K737, K754, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K867. 3 / 3
3 |

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Mutated USP8 leads to the deubiquitination of EGFR. 3 / 3
| 3

reach
"The identified USP8 mutants increase EGFR deubiquitination to inhibit EGF induced EGFR downregulation, leading to augmented and more sustained EGFR signaling."

reach
"USP8 mutations lead to enhanced deubiquitination of the epidermal growth factor receptor (EGFR) and result in an imbalance in EGFR signalling, accompanied by excessive activation of ACTH production and cell growth."

reach
"USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells."
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, K929, Y1092, Y1016, K716, Y1197, and Y1069 on K970. 3 / 3
3 |

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USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K754, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K737. 3 / 3
3 |

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USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K754. 3 / 3
3 |

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USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K929. 3 / 3
3 |

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USP8 in the endosome deubiquitinates EGFR in the endosome. 1 / 1
| 1

trips
"We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes."
USP8 binds EGFR.
7 | 1 9 14
7 | 1 7 14

reach
"In EGF stimulated cells, UBPY underwent ubiquitination and bound to EGFR."

sparser
"UBPY binds to endocytosed EGFR and deubiquitinates it on early endosomes [10] ."

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sparser
"However, the level of UBPY S680A binding to EGFR was comparable to that of wild-type UBPY ( Supplementary Fig. S2 )."

sparser
"When overexpressed in HeLa cells, USP8 mutations were associated with reduced EGFR ubiquitination and degradation as compared to WT controls."

reach
"We therefore examined whether the binding of UBPY to EGFR is indirect and mediated by 14-3-3 proteins which normally exist as a dimer [18]."

sparser
"We therefore examined whether the binding of UBPY to EGFR is indirect and mediated by 14-3-3 proteins which normally exist as a dimer [18] ."

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trips
"In EGF-stimulated cells, UBPY underwent ubiquitination and bound to EGFR."

sparser
"Overall, these results support and extend our previous model that Usp8 and EGFR associate via multiple molecular interactions."
USP8-S680A binds EGFR. 2 / 2
| 2

reach
"Immunoblotting of the precipitates with anti-FLAG antibody showed that wild-type UBPY and UBPY S680A bind to EGFR with similar efficiency upon EGF stimulation, indicating that the interaction between [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"However, the level of UBPY S680A binding to EGFR was comparable to that of wild-type UBPY."
USP8 activates EGFR.
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USP8 activates EGFR. 10 / 22
| 20

reach
"This current study showed that the EGFR, PI3K, and NF-κB signaling is downregulated and upregulated in PCa by USP8 silencing and overexpressing, respectively ( Figure 4 )."

reach
"Other studies have suggested that mutations in USP8 reduce the degradation of EGFR, such as HER-2 and HER-3, thereby promoting tumor progression."

reach
"Nevertheless, both AMSH [31, 34, 35] and UBPY [32, 33, 36-38] have been reported to increase EGFR down-regulation."

reach
"USP8 knockdown leads to reduce EGFR protein and inhibits ACTH secretion."

reach
"Whereas USP8 variants increase EGFR signaling in cultured cells, such an effect has not been consistently shown in vivo, suggesting that the effect is small or temporary or that other factors [XREF_BIBR] are involved in increased ACTH production and/or proliferation of USP8 mutation positive tumors."

reach
"USP8 depletion inhibits EGFR degradation and causes accumulation of ubiquitinated proteins on enlarged endosomes 11, 12."

reach
"These binding reactions provide a scenario in which UBPY could aid transit of EGFR to ESCRT-III by helping to displace STAM2 from HD-PTP."

reach
"Our previous results have shown that Usp8 tyrosine phosphorylation upon EGF induced stimulation is EGFR- and Src- tyrosine kinase dependent [41]."

reach
"One report concludes that UBPY negatively regulates degradation of the epidermal growth factor receptor (EGFR), which is downregulated via MVB sorting and lysosomal degradation."

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."
Mutated USP8 activates EGFR. 7 / 7
| 7

reach
"We found that USP8 mutated PAs have a higher incidence of EGFR expression, increased EGFR protein abundance and activation of downstream Erk1/2, indicating that USP8 mutations enhance EGFR signaling in tumors."

reach
"USP8 mutations, detected in up to two-thirds of Cushing disease, may underlie the increase in EGFR signalling in these tumours."

reach
"The USP8 mutation (14-3-3 somatic mutations) induces corticotroph EGFR adenoma signaling by rescuing EGFR from lysosomal degradation and enhancing EGFR accumulation (9)."

reach
"Previous studies have demonstrated that the USP8 mutation causes corticotroph adenomas mainly through activating the EGFR–MAPK signal cascades ."

reach
"In human corticotroph primary cultures, treatment with the pan-ErbB TKI canertinib as well as the EGFR TKI gefitinib suppresses POMC mRNA, and USP8 mutations, detected in up to two-thirds of CD, may underlie the increase in EGFR signaling in these tumors."

reach
"The USP8 mutation (14-3-3 somatic mutations) inhibits EGFR degradation, enhances EGFR accumulation, and consequently, likely induces corticotroph EGFR tumor signaling."

reach
"Considering that activation of EGFR-MAPK signaling induces p27 (Kip1) degradation, and p27 (Kip1)-deficient mice develop corticotropinoma XREF_BIBR, XREF_BIBR, we speculate that through activating EGFR signaling USP8 mutation accelerates p27 (Kip1) degradation, representing an important molecular mechanism underlying ACTH hyperproduction (XREF_FIG)."
USP8 bound to SH3 domain and CHMP4B activates EGFR. 1 / 1
| 1

reach
"Such polarity extends to include the deubiquitinase UBPY (Ub-protease Y, equivalent to yeast Doa4; Table 1), which binds to both CHMP4B and to the STAM SH3 domain [74], and supports HD-PTP-dependent EGFR sorting [54,75]."
USP8 inhibits EGFR.
| 7
USP8 inhibits EGFR. 7 / 9
| 7

reach
"In keeping with this intermediate phenotype, UBPY depletion partially reduced the interaction of EGFR with ESCRT-III."

reach
"By the same mechanism, USP8 also directs the trafficking and lysosomal degradation of CXCR4 [XREF_BIBR], MET and epidermal growth factor receptor [XREF_BIBR, XREF_BIBR], implying that its loss consequent to increased RNF41 abundance would prolong and potentially amplify invasion signaling by these receptors."

reach
"By removing the lysosomal sorting signal, UBPY negatively regulates the downregulation of EGFR [10]."

reach
"While one report suggests that Usp8 inhibits EGFR degradation [25], we and others have demonstrated that Usp8 promotes EGFR degradation [21,26]."

reach
"While some reports suggest that Usp8 inhibits EGFR degradation [40], we and others demonstrated that Usp8 stimulates EGFR degradation [41,42]."

reach
"USP8 has been shown to have opposing effects on EGF receptor degradation by either directly deubiquitinating receptors to prevent their degradation, or by deubiquitinating ESCRT complex proteins to stabilize them and thus promote EGF receptor degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR]."

reach
"Depletion of USP8 with siRNA inhibits EGFR activation and increases EGFR degradation [32], similar to the effect of depleting SEPW1, and suggests the possibility SEPW1 might regulate USP8."
USP8 increases the amount of EGFR.
| 7
USP8 increases the amount of EGFR. 7 / 7
| 7

reach
"Consistently, the expression of EGFR was decreased by genetic silencing of USP8."

reach
"Similar to Marks et al., we found an elevated EGFR expression in DU145 and PC3 which was severely increased upon USP8 overexpression and docetaxel treatment, whereas silencing USP8 significantly reduced EGFR expression and thereby decreased NF-kB signal activation."

reach
"Western blotting confirmed that knockdown of USP8 not only reduced RTK phosphorylation, but also the total levels of EGFR, ERBB2, ERBB3, and MET in H1975 and H1650 cells (XREF_FIG)."

reach
"Taken together, our findings demonstrate for the first time that inhibition of USP8 down-regulates the total protein levels of EGFR, ERBB2, ERBB3, and MET, and effectively attenuates related RTK signaling pathways."

reach
"USP8 knockdown in primary ACTH secreting tumor cells, however, reduced ACTH secretion and EGFR levels, suggesting that inhibition of USP8 activity may be an effective treatment strategy for CD."

reach
"Thereby, together with these data, it can be concluded that the elevated level of USP8 not only increases the expression of EGFR, PI3K, and P-Akt but also might increase the PI3K and P-Akt expression over EGFR silencing where the PI3K and P-Akt well established the downstream target of EGFR ( Figures 6C, D )."

reach
"Moreover, USP8 knockdown reduced EGFR protein level in USP8 mutated tumor cells (XREF_SUPPLEMENTARY)."
USP8 ubiquitinates EGFR.
| 3
USP8 leads to the ubiquitination of EGFR. 2 / 2
| 2

reach
"Cell 16, 5163-5174) concludes that UBPY negatively regulates EGFR degradation by de-ubiquitinating the EGFR on endosomes, another report (Row, P. E., Prior, I. A., McCullough, J., Clague, M. J., and Urbe, S. (2006) J. Biol."

reach
"We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes."
Modified USP8 leads to the ubiquitination of EGFR. 1 / 1
| 1

reach
"Together, the results in Figs. 3 and 4, and S3 suggested that the binding of 14-3-3s inhibits the DUB activity of UBPY in vitro.We have shown that the overexpression of UBPY causes a reduction in the [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 decreases the amount of EGFR.
| 1
USP8 decreases the amount of EGFR. 1 / 3
| 1

reach
"Importantly, USP8 inactivation attenuated ACTH secretion and EGFR expression in primary tumor cells."
USP8 affects SMO
1 | 61 26
USP8 binds SMO.
| 15 26
| 15 21

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."

reach
"The finding that USP8 interacted with Smo led to the hypothesis that Hh might control the accessibility of Smo to the DUB."

sparser
"Overall, these results together imply that Rack1 stabilizes Smo and increases Smo cell membrane localization through promoting SmoUsp8 interaction."

reach
"These data suggest that phosphorylation of Smo promotes the formation of a Smo and USP8 complex, which may amplify the Hh stimulation and lead to the activation of Smo."

reach
"However, we found that UBPY decreases Smo ubiquitination regardless of the Hh signaling states and that the association between UBPY and Smo is not significantly affected by either Hh stimulation or Smo phosphorylation, suggesting that Smo deubiquitination by UBPY is unlikely to be a major mechanism by which Hh inhibits Smo ubiquitination, although we can not rule out the possibility that Hh regulates UBPY binding to Smo in a subtle way that escaped the detection by our coimmunoprecipitation assay."

sparser
"Furthermore we show that Hh can enhance the interaction between Smo and USP8."

sparser
"In addition, we found, in an immunoprecipitation experiment, that a substantial amount of Smo SD123 interacted with USP8 ( xref , lane 2, top panel)."

sparser
"We then carried out coimmunoprecipitation assays to determine whether UBPY physically interacts with Smo."

reach
"However, we found that Hrs blocks Smo phosphorylation (XREF_FIG), whereas USP8 does not XREF_BIBR, suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"Intriguingly, with Hh stimulation, Rack1 dissociated from Ci–Cos2 complex and formed a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
SMO binds USP8 and RACK1. 3 / 3
| 3

sparser
"In the presence of Hh, Hh dissociates Ci–Rack1 interaction, and promotes Rack1 forming a trimeric complex with Usp8 and Smo, resulting in Smo deubiquitination and cell surface accumulation (Fig.  xref )."

sparser
"The two-step co-IP assay showed that Usp8, Rack1, and Smo formed a trimeric complex (Fig.  xref )."

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
SMO binds USP8 and HGS. 2 / 2
| 2

sparser
"However, we found that Hrs blocks Smo phosphorylation ( xref ), whereas USP8 does not xref , suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"It is possible that Hrs competes with USP8 for binding Smo, as Hrs and USP8 directly interact with the same domain of Smo."
USP8 activates SMO.
| 11
USP8 activates SMO. 9 / 18
| 9

reach
"The stimulation of Hh promotes Smo deubiquitination by ubiquitin specific protease 8 (USP8), which blocks Smo endocytosis and enhances Smo cell surface accumulation XREF_BIBR XREF_BIBR."

reach
"Overexpression of USP8 caused an elevation of Smo in both A- and P-compartment cells but did not ectopically activate Hh target genes, such as ptc, in A-compartment cells located away from the A/P boundary (XREF_FIG)."

reach
"We next wished to assess whether the accumulation of Smo induced by the overexpression of USP8 or the inactivation of Shi was due to changes in the cell surface accumulation of Smo."

reach
"USP8 Promotes Smo Signaling Activity."

reach
"USP8 Promotes Smo Accumulation in Wing Imaginal Discs."

reach
"It is also possible that USP8 promotes Smo recycling to the cell surface."

reach
"In addition, a gain-of-function experiment showed that the overexpression of USP8 caused an accumulation of Smo in both A- and P-compartment cells (XREF_FIG) and caused anterior expansion of ptc-lacZ in cells that received Hh (XREF_FIG)."

reach
"We revealed that overexpression of usp8 blocked rack1 RNAi induced Smo degradation, suggesting that Rack1 positively regulates Smo possibly through Usp8."

reach
"These data suggest that USP8 promotes the cell surface accumulation of Smo, and that Shi mediates Smo endocytosis."
Modified USP8 activates SMO. 2 / 2
| 2

reach
"The overexpression of USP8 down-regulated Smo ubiquitination and increased Smo accumulation."

reach
"Moreover, overexpression of USP8 prevents Smo ubiquitination and elevates Smo accumulation, leading to increased Hh signaling activity."
USP8 deubiquitinates SMO.
1 | 18
USP8 deubiquitinates SMO. 10 / 14
1 | 13

reach
"In addition, it has been reported that the deubiquitinase Usp8 could deubiquitinate Smo to influence Hh signaling activity."

reach
"Although our observations support the notion that USP8 deubiquitinates Smo and prevents localization to early endosomes, we are not suggesting that USP8 play an exclusive role in the inhibition of Smo endocytosis."

reach
"As shown in XREF_FIG, USP8, but not the other DUBs, reduced the ubiquitination of Myc-Smo."

reach
"In addition, it has been reported that the deubiquitinase Usp8 could deubiquitinate Smo to influence Hh signaling activity (Li et al., 2012; Xia et al., 2012)."

reach
"Hh promotes the formation of a Smo and USP8 complex, and USP8 further promotes the accumulation of Smo at the cell surface and prevents localization to the early endosomes by deubiquitinating Smo, leading to increased Hh signaling activity."

reach
"Inactivation of the ubiquitin activating enzyme-Uba1 promotes Smo accumulation on the cell surface and Hh signaling activation, and USP8 decreases Smo ubiquitination to promote its cell surface accumulation in the absence or presence of Hh."

reach
"Using an in vivo RNAi screen, we identified ubiquitin specific protease 8 (USP8) as a deubiquitinase that down-regulates Smo ubiquitination."

reach
"In addition, we provide evidence that the non visual beta-arrestin Krz acts in parallel with Smo ubiquitination to promote its internalization and that Smo ubiquitination is antagonized by the deubiquitinating enzyme UBPY."

reach
"However, we found that UBPY decreases Smo ubiquitination regardless of the Hh signaling states and that the association between UBPY and Smo is not significantly affected by either Hh stimulation or Smo phosphorylation, suggesting that Smo deubiquitination by UBPY is unlikely to be a major mechanism by which Hh inhibits Smo ubiquitination, although we can not rule out the possibility that Hh regulates UBPY binding to Smo in a subtle way that escaped the detection by our coimmunoprecipitation assay."
Modified USP8 leads to the deubiquitination of SMO. 4 / 4
| 4

reach
"Consistent with UBPY being able to counteract Smo ubiquitination independent of Hh signaling states, overexpression of UBPY reduced Smo ubiquitination in S2 cells both in the absence and presence of Hh (XREF_FIG)."

reach
"Moreover, overexpression of USP8 prevents Smo ubiquitination and elevates Smo accumulation, leading to increased Hh signaling activity."

reach
"Overexpression of Flag-USP8 in S2 cells reduced Smo ubiquitination (XREF_FIG, lane 3, top panel), whereas knockdown of USP8 by RNAi enhanced the levels of ubiquitinated Smo (XREF_FIG, lane 2, top panel), which was consistent with the data from the screen."

reach
"The overexpression of USP8 down-regulated Smo ubiquitination and increased Smo accumulation."
Sumoylated USP8 leads to the deubiquitination of SMO. 1 / 1
| 1

reach
"SUMOylation is triggered via dissociation of Smo from the de-sumoylating enzyme Ulp1 and was shown to allow recruitment of USP8 to antagonize Smo ubiquitination and degradation [56,84,85]."
USP8 inhibits SMO.
| 3
USP8 inhibits SMO. 3 / 10
| 3

reach
"USP8 Prevents the Localization of Smo to the Early Endosome."

reach
"The stimulation of Hh promotes Smo deubiquitination by ubiquitin specific protease 8 (USP8), which blocks Smo endocytosis and enhances Smo cell surface accumulation XREF_BIBR XREF_BIBR."

reach
"Moreover, we found that USP8 prevents Smo localization to early endosomes that are labeled with Rab5."
USP8 ubiquitinates SMO.
| 7
USP8 leads to the ubiquitination of SMO. 7 / 7
| 7

reach
"Inactivation of USP8 increases Smo ubiquitination and attenuates Hh induced Smo accumulation, leading to decreased Hh signaling activity."

reach
"As shown in XREF_FIG, inactivation of USP8 in S2 cells by RNAi dramatically enhanced the levels of Smo ubiquitination (XREF_FIG, lane 4, compare to lane 2, top panel), whereas the reduction of other DUBs by RNAi did not, suggesting that the inhibition of Smo accumulation by USP8 RNAi in wing discs was due to the increase in Smo ubiquitination."

reach
"We also provide evidence that the non visual beta-arrestin Kurtz (Krz) acts in parallel with Smo ubiquitination to control Smo cell surface expression, and that the deubiquitinating enzyme UBPY promotes Smo cell surface expression by counteracting Smo ubiquitination."

reach
"From this screen, we found that RNAi of the Drosophila UBPY and USP8 significantly increased the basal levels of Smo ubiquitination (XREF_SUPPLEMENTARY)."

reach
"We also show that inactivation of USP8 by RNAi or by overexpressing a dominant negative form of USP8 increases Smo ubiquitination in S2 cells and prevents Smo accumulation in wing discs."

reach
"Consistent with these data, the overexpression of USP8 reduced Smo SD123 ubiquitination, whereas the inactivation of USP8 increased Smo ubiquitination (XREF_FIG)."

reach
"We also found that inactivation of UBPY by RNAi increased Smo ubiquitination in the presence of Hh (XREF_FIG), suggesting that UBPY counteracts Smo ubiquitination in both Hh signaling " off " and " on " states."
USP8 increases the amount of SMO.
| 5
USP8 increases the amount of SMO. 3 / 3
| 3

reach
"UBPY may modulate Smo cell surface expression by attenuating Smo endocytosis and/or promoting Smo recycling (XREF_FIG)."

reach
"We also provide evidence that the non visual beta-arrestin Kurtz (Krz) acts in parallel with Smo ubiquitination to control Smo cell surface expression, and that the deubiquitinating enzyme UBPY promotes Smo cell surface expression by counteracting Smo ubiquitination."

reach
"Our explanation is that the increase in Smo levels that was induced by USP8 was still inhibited by Ptc, since we found that USP8 induced more severe overgrowth phenotypes in the ptc mutant background (XREF_FIG)."
Modified USP8 increases the amount of SMO. 2 / 2
| 2

reach
"However, although the overexpression of USP8 increased the levels of Smo in vivo, it failed to induce Hh target gene expression in A-compartment cells located away from the A/P boundary."

reach
"Overexpression of USP8 elevated the level of Smo but did not induce ectopic Hh signaling activity in A compartment cells located away from the A/P boundary."
USP8 decreases the amount of SMO.
| 2
USP8 decreases the amount of ubiquitinated SMO. 1 / 1
| 1

reach
"Overexpression of Flag-USP8 in S2 cells reduced Smo ubiquitination (XREF_FIG, lane 3, top panel), whereas knockdown of USP8 by RNAi enhanced the levels of ubiquitinated Smo (XREF_FIG, lane 2, top panel), which was consistent with the data from the screen."
Modified USP8 decreases the amount of ubiquitinated SMO. 1 / 1
| 1

reach
"In agreement with this hypothesis, the overexpression of HA-USP8 reversed the effects of Flag-USP8C> S and again reduced the levels of ubiquitinated Smo (XREF_FIG, lane 4, top panel)."
USP8 affects RNF41
1 5 1 1 | 34 32
USP8 binds RNF41.
5 1 | 27 32
5 1 | 9 19

sparser
"Lastly, to ambiguously demonstrate the interactions between Nrdp1 and USP8 and between USP8 and HIF-1α in OGD-treated neurons, we performed co-immunoprecipitation experiments."

sparser
"Nrdp1 and USP8 could be coimmunoprecipitated, and in transfected cells USP8 specifically bound to Nrdp1 but not cbl, a RING finger E3 ligase involved in ligand-stimulated epidermal growth factor receptor down-regulation."

sparser
"As expected, Clec16a- specific shRNA reduced Nrdp1-USP8 binding in situ ( xref )."

sparser
"To assess the role of Clec16a-mediated ubiquitination on formation of the β-cell mitophagy complex, we utilized a proximity ligation assay (PLA) to visualize Nrdp1-USP8 association in situ after lenalidomide treatment ( xref )."

reach
"While Clec16a enhanced Nrdp1-USP8 complex assembly, addition of the ubiquitin KO mutant reduced Nrdp1 levels as well as Nrdp1 interaction with both Clec16a and USP8 (Fig. 4E)."

reach
"USP8 interactions with Nrdp1 and BRUCE."

sparser
"Indeed, we found that the interaction of NRDP1 and USP8 was decreased following a 48 h exposure to palmitate and high glucose in both beta cell lines as well as primary human beta cells by PLA ( xref and reference xref )."

sparser
"While Clec16a enhanced Nrdp1-USP8 complex assembly, addition of the ubiquitin KO mutant reduced Nrdp1 levels as well as Nrdp1 interaction with both Clec16a and USP8 ( xref )."

No evidence text available

sparser
"Also, RNF41 can interact with the deubiquitylating enzyme USP8 (also called UBPy), which is required for maintenance of ESCRT-0 stability and endosomal sorting of ErbB3 and EGFR ( xref ; xref )."
| 18 10

reach
"Furthermore, we observed that both Nrdp1 stability and ubiquitination were reduced in Min6 β-cells after palmitate treatment (Fig. 6D), thus demonstrating effects consistent with impact on the Clec16a pathway to maintain the upstream mitophagy complex.To determine whether glucolipotoxicity affects Clec16a to impact formation of the Clec16a-Nrdp1-USP8 complex, we overexpressed Clec16a in palmitate-treated Min6 β-cells."

reach
"Further, we observe that diabetogenic metabolic stressors, including elevated glucose and fatty acids, destabilize the CLEC16A, RNF41, and USP8 complex and lead to beta-cell apoptosis."

reach
"Given our findings suggesting that both Nrdp1 stability and ubiquitination regulate formation of the Clec16a-Nrdp1-USP8 complex, we next measured Nrdp1 levels after palmitate treatment in primary islets."

reach
"We next assessed the role of Nrdp1 ubiquitination on formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Previous observations of defective mitochondrial integrity after glucolipotoxicity (7,36), coupled with our findings here of glucolipotoxicity-mediated destabilization of the Clec16a-Nrdp1-USP8 complex, could inspire future in vivo studies to evaluate the importance of dysfunctional mitophagy to β-cell failure in diabetes."

reach
"To determine the importance of maintenance of the Clec16a-Nrdp1-USP8 complex to β-cell survival during glucolipotoxicity, we assessed β-cell apoptosis by cleaved caspase-3 levels after Clec16a overexpression."

sparser
"Given the importance of ubiquitination to Clec16a-Nrdp1-USP8 complex assembly, we hypothesized that specific ubiquitination of Nrdp1 may influence formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Thus, the beta-cell mitophagy pathway requires ubiquitin signals to stabilize the CLEC16A, RNF41, and USP8 complex and maintain mitochondrial quality control."

reach
"While the dynamics of the Clec16a-Nrdp1-USP8 complex are still a mystery, it is clear that Clec16a-mediated ubiquitination orchestrates mitophagic flux in β-cells.Our discovery of Clec16a as an E3 ligase, whose function is inhibited by lenalidomide, expands our insight into its functional role in mitophagy."

sparser
"Furthermore, Clec16a-mediated Nrdp1 ubiquitination is essential for assembly of the Clec16a-Nrdp1-USP8 complex and preservation of β-cell function ( xref )."

sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."
| 1

sparser
"There was evidence that Magel2 was involved in the leptin-POMC of the hypothalamus to maintain the energy balance of the body.[ xref ]Wijesuriya et al have found that MAGEL2 and Necdin connected leptin receptor (LepR) to the USP8-RNF41 ubiquitin complex through the LepR adapter protein, IRS4."
USP8 binds BIRC6 and RNF41. 1 / 1
| 1

sparser
"USP8 interactions with Nrdp1 and BRUCE."
USP8 activates RNF41.
| 4
USP8 activates RNF41. 4 / 9
| 4

reach
"We tested the importance of USP8 to Clec16a-mediated Nrdp1 stability by both gain- and loss-of-function approaches."

reach
"Our results indicate that Nrdp1 is a specific target for the USP8 deubiquitinating enzyme and are consistent with a model where USP8 augments Nrdp1 activity by mediating its stabilization."

reach
"Since Nrdp1 targets USP8 for ubiquitylation, we speculated that overexpression of Nrdp1 could enhance protein ubiquitylation and USP8 degradation in PC12 cells."

reach
"USP8 markedly enhanced the stability of Nrdp1, and a point mutant that disrupts USP8 catalytic activity destabilized endogenous Nrdp1."
USP8 deubiquitinates RNF41.
1 1 | 2
USP8 deubiquitinates RNF41. 3 / 3
1 | 2

reach
"We found that the carboxy terminal domain of Nrdp1 binds to the rhodanese domain of USP8, and that USP8 very efficiently deubiquitinates and stabilizes Nrdp1."

reach
"USP8 deubiquitinates STAM, preventing its degradation by the proteasome [XREF_BIBR], and Nrdp1, an E3 required for the lysosomal degradation of EGFR family members ErbB3 and ErbB4 [XREF_BIBR]."
Threonine-phosphorylated USP8 deubiquitinates RNF41. 1 / 1
1 |

No evidence text available
USP8 ubiquitinates RNF41.
| 1
USP8 leads to the ubiquitination of RNF41. 1 / 1
| 1

reach
"In the presence of the ErbB3 ligand neuregulin-1, AKT phosphorylates the USP8 DUB at T907 and contributes to USP8 stability, which, in turn, suppresses the ubiquitination and degradation of Nrdp1."
RNF41 affects USP8
5 1 | 1 33 33
RNF41 binds USP8.
5 1 | 27 32
5 1 | 9 19

sparser
"Lastly, to ambiguously demonstrate the interactions between Nrdp1 and USP8 and between USP8 and HIF-1α in OGD-treated neurons, we performed co-immunoprecipitation experiments."

sparser
"Nrdp1 and USP8 could be coimmunoprecipitated, and in transfected cells USP8 specifically bound to Nrdp1 but not cbl, a RING finger E3 ligase involved in ligand-stimulated epidermal growth factor receptor down-regulation."

sparser
"As expected, Clec16a- specific shRNA reduced Nrdp1-USP8 binding in situ ( xref )."

sparser
"To assess the role of Clec16a-mediated ubiquitination on formation of the β-cell mitophagy complex, we utilized a proximity ligation assay (PLA) to visualize Nrdp1-USP8 association in situ after lenalidomide treatment ( xref )."

reach
"While Clec16a enhanced Nrdp1-USP8 complex assembly, addition of the ubiquitin KO mutant reduced Nrdp1 levels as well as Nrdp1 interaction with both Clec16a and USP8 (Fig. 4E)."

reach
"USP8 interactions with Nrdp1 and BRUCE."

sparser
"Indeed, we found that the interaction of NRDP1 and USP8 was decreased following a 48 h exposure to palmitate and high glucose in both beta cell lines as well as primary human beta cells by PLA ( xref and reference xref )."

sparser
"While Clec16a enhanced Nrdp1-USP8 complex assembly, addition of the ubiquitin KO mutant reduced Nrdp1 levels as well as Nrdp1 interaction with both Clec16a and USP8 ( xref )."

No evidence text available

sparser
"Also, RNF41 can interact with the deubiquitylating enzyme USP8 (also called UBPy), which is required for maintenance of ESCRT-0 stability and endosomal sorting of ErbB3 and EGFR ( xref ; xref )."
| 18 10

reach
"Furthermore, we observed that both Nrdp1 stability and ubiquitination were reduced in Min6 β-cells after palmitate treatment (Fig. 6D), thus demonstrating effects consistent with impact on the Clec16a pathway to maintain the upstream mitophagy complex.To determine whether glucolipotoxicity affects Clec16a to impact formation of the Clec16a-Nrdp1-USP8 complex, we overexpressed Clec16a in palmitate-treated Min6 β-cells."

reach
"Further, we observe that diabetogenic metabolic stressors, including elevated glucose and fatty acids, destabilize the CLEC16A, RNF41, and USP8 complex and lead to beta-cell apoptosis."

reach
"Given our findings suggesting that both Nrdp1 stability and ubiquitination regulate formation of the Clec16a-Nrdp1-USP8 complex, we next measured Nrdp1 levels after palmitate treatment in primary islets."

reach
"We next assessed the role of Nrdp1 ubiquitination on formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Previous observations of defective mitochondrial integrity after glucolipotoxicity (7,36), coupled with our findings here of glucolipotoxicity-mediated destabilization of the Clec16a-Nrdp1-USP8 complex, could inspire future in vivo studies to evaluate the importance of dysfunctional mitophagy to β-cell failure in diabetes."

reach
"To determine the importance of maintenance of the Clec16a-Nrdp1-USP8 complex to β-cell survival during glucolipotoxicity, we assessed β-cell apoptosis by cleaved caspase-3 levels after Clec16a overexpression."

sparser
"Given the importance of ubiquitination to Clec16a-Nrdp1-USP8 complex assembly, we hypothesized that specific ubiquitination of Nrdp1 may influence formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Thus, the beta-cell mitophagy pathway requires ubiquitin signals to stabilize the CLEC16A, RNF41, and USP8 complex and maintain mitochondrial quality control."

reach
"While the dynamics of the Clec16a-Nrdp1-USP8 complex are still a mystery, it is clear that Clec16a-mediated ubiquitination orchestrates mitophagic flux in β-cells.Our discovery of Clec16a as an E3 ligase, whose function is inhibited by lenalidomide, expands our insight into its functional role in mitophagy."

sparser
"Furthermore, Clec16a-mediated Nrdp1 ubiquitination is essential for assembly of the Clec16a-Nrdp1-USP8 complex and preservation of β-cell function ( xref )."

sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."
| 1

sparser
"There was evidence that Magel2 was involved in the leptin-POMC of the hypothalamus to maintain the energy balance of the body.[ xref ]Wijesuriya et al have found that MAGEL2 and Necdin connected leptin receptor (LepR) to the USP8-RNF41 ubiquitin complex through the LepR adapter protein, IRS4."
USP8 binds BIRC6 and RNF41. 1 / 1
| 1

sparser
"USP8 interactions with Nrdp1 and BRUCE."
RNF41 ubiquitinates USP8.
| 1 1 1
RNF41 ubiquitinates USP8. 3 / 3
| 1 1 1

reach
"Mechanistically, the E3 ligase Nrdp1 indirectly destabilizes the ESCRT-0 complex by ubiquitinating and suppressing USP8."

sparser
"We further demonstrated that this results from RNF41-dependent ubiquitination and suppression of the deubiquitinating enzyme USP8, which abrogates ESCRT-0 functionality and accounts for the rerouting of cytokine receptors ( xref )."

trips
"RNF41 redistributes and ubiquitylates USP8, and reduces USP8 levels."
RNF41 inhibits USP8.
| 2
RNF41 inhibits USP8. 2 / 3
| 2

reach
"When Nrdp1 is increased, more USP8 will be degraded by Nrdp1, and as a return, less USP8 will make Nrdp1 unstable, resulting in less Nrdp1 and more USP8 in the cells."

reach
"RNF41 also negatively regulates the stability of the ubiquitin isopeptidase USP8, a regulator of JAK2 associated cytokine receptor sorting and processing : elevated RNF41 destabilizes the endosomal-sorting-complexes-required-for-transport (ESCRT) -0 complex (Hrs and signal-transducing-and adapter-molecule (STAM) -1 or STAM2), which results in cargo arriving at sorting endosomes being routed to recycling endosomes rather than to lysosomes [XREF_BIBR]."
RNF41 activates USP8.
| 2
RNF41 activates USP8. 2 / 2
| 2

reach
"Since Nrdp1 targets USP8 for ubiquitylation, we speculated that overexpression of Nrdp1 could enhance protein ubiquitylation and USP8 degradation in PC12 cells."

reach
"Nrdp1 activates NRG-1beta-induced HER3 degradation [XREF_BIBR] and USP8 prevents Nrdp1 auto-ubiquitination [XREF_BIBR], with a strong correlation between USP8 expression and Nrdp1 stabilization [XREF_BIBR]."
RNF41 deubiquitinates USP8.
| 1
Modified RNF41 leads to the deubiquitination of USP8. 1 / 1
| 1

reach
"Since Nrdp1 targets USP8 for ubiquitylation, we speculated that overexpression of Nrdp1 could enhance protein ubiquitylation and USP8 degradation in PC12 cells."
EGFR affects USP8
2 7 | 1 26 24
EGFR binds USP8.
7 | 1 9 14
7 | 1 7 14

reach
"In EGF stimulated cells, UBPY underwent ubiquitination and bound to EGFR."

sparser
"UBPY binds to endocytosed EGFR and deubiquitinates it on early endosomes [10] ."

No evidence text available

sparser
"However, the level of UBPY S680A binding to EGFR was comparable to that of wild-type UBPY ( Supplementary Fig. S2 )."

sparser
"When overexpressed in HeLa cells, USP8 mutations were associated with reduced EGFR ubiquitination and degradation as compared to WT controls."

reach
"We therefore examined whether the binding of UBPY to EGFR is indirect and mediated by 14-3-3 proteins which normally exist as a dimer [18]."

sparser
"We therefore examined whether the binding of UBPY to EGFR is indirect and mediated by 14-3-3 proteins which normally exist as a dimer [18] ."

No evidence text available

trips
"In EGF-stimulated cells, UBPY underwent ubiquitination and bound to EGFR."

sparser
"Overall, these results support and extend our previous model that Usp8 and EGFR associate via multiple molecular interactions."
USP8-S680A binds EGFR. 2 / 2
| 2

reach
"Immunoblotting of the precipitates with anti-FLAG antibody showed that wild-type UBPY and UBPY S680A bind to EGFR with similar efficiency upon EGF stimulation, indicating that the interaction between [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"However, the level of UBPY S680A binding to EGFR was comparable to that of wild-type UBPY."
EGFR phosphorylates USP8.
2 | 5 7
EGFR phosphorylates USP8 on Y717. 5 / 5
1 | 2 2

reach
"Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr 717 and Tyr 810 in RPE1 cells."

sparser
"USP8 phosphorylation on Tyr717 and Tyr810 by EGFR kinase elevates its activity and then activates an inhibitory mechanism of ciliogenesis, i.e., EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase [ xref ]."

No evidence text available

sparser
"Additionally, EGFR kinase-induced phosphorylation of USP8 at Tyr717 and Tyr810 residues elevates its activity and activates the EGF receptor kinase-mediated inhibition of ciliogenesis."

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC
EGFR phosphorylates USP8 on Y810. 5 / 5
1 | 2 2

reach
"Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr 717 and Tyr 810 in RPE1 cells."

sparser
"USP8 phosphorylation on Tyr717 and Tyr810 by EGFR kinase elevates its activity and then activates an inhibitory mechanism of ciliogenesis, i.e., EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase [ xref ]."

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC

No evidence text available

sparser
"Additionally, EGFR kinase-induced phosphorylation of USP8 at Tyr717 and Tyr810 residues elevates its activity and activates the EGF receptor kinase-mediated inhibition of ciliogenesis."
EGFR phosphorylates USP8. 4 / 4
| 1 3

reach
"To validate the effect of EGFR phosphorylation of USP8 in vitro, we used also non tagged USP8 because GST-USP8 had a significantly higher DUB activity than non tagged USP8 in non phosphorylated forms."

sparser
"To validate the effect of EGFR phosphorylation of USP8 in vitro, we used also non-tagged USP8 because GST-USP8 had a significantly higher DUB activity than non-tagged USP8 in non-phosphorylated forms (Supplementary Fig.  xref )."

sparser
"Overall, we have provided strong evidence for ligand-induced ERBB- and SRC family kinase-dependent tyrosine phosphorylation of Usp8 1–504."

sparser
"Importantly, GST-EGFR phosphorylated non-tagged USP8 and elevated its DUB activity toward ubiquitin oligomers (Fig.  xref ; lanes 1–3), but GST-EGFR did not activate GST-USP8 (Supplementary Fig.  xref )."
EGFR dephosphorylates USP8.
| 7
EGFR dephosphorylates USP8 on Y810. 3 / 3
| 3

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC

reach
"Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr 717 and Tyr 810 in RPE1 cells."

reach
"In contrast, Kasahara et al. [88] reported that EGFR kinase suppresses ciliogenesis by phosphorylating USP8 on Tyr717 and Tyr810 enhancing the deubiquitinase activity."
EGFR dephosphorylates USP8 on Y717. 3 / 3
| 3

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC

reach
"Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr 717 and Tyr 810 in RPE1 cells."

reach
"In contrast, Kasahara et al. [88] reported that EGFR kinase suppresses ciliogenesis by phosphorylating USP8 on Tyr717 and Tyr810 enhancing the deubiquitinase activity."
EGFR leads to the dephosphorylation of USP8 on tyrosine. 1 / 1
| 1

reach
"This model is supported by our current findings that TGFalpha stimulation of EGFR and EGF stimulation of ERBB2 [52], conditions that are associated with enhanced endosomal recycling and decreased MVB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
EGFR activates USP8.
| 4 3
EGFR activates USP8. 7 / 7
| 4 3

reach
"Most importantly, epidermal growth factor receptor (EGFR) kinase activated USP8 by phosphorylating Tyr 717 and Tyr 810."

sparser
"Importantly, GST-EGFR phosphorylated non-tagged USP8 and elevated its DUB activity toward ubiquitin oligomers (Fig.  xref ; lanes 1–3), but GST-EGFR did not activate GST-USP8 (Supplementary Fig.  xref )."

sparser
"EGFR activates USP8 by phosphorylating Tyr-717 and Tyr-810."

sparser
"Taken together, EGFR activates USP8 by directly phosphorylating Tyr-717 and −810 in vitro."

reach
"EGFR activates USP8 by phosphorylating Tyr 717 and Tyr 810."

reach
"EGFR activation causes USP8 to become phosphorylated and to associate with EGFR on endosomes where it dynamically regulates EGFR ubiquitination state during trafficking."

reach
"Taken together, EGFR activates USP8 by directly phosphorylating Tyr 717 and -810 in vitro."
EGFR deubiquitinates USP8.
| 1
EGFR deubiquitinates USP8. 1 / 1
| 1

reach
"Although still a matter of debate, EGFR deubiquitination by the ESCRT-associated deubiquitinating (DUB) enzyme UBPY (ubiquitin-specific protease 8) appears to facilitate the transfer of activated EGFRs from early ubiquitin-binding ESCRT complexes (ESCRT-0, -I, -II) to ESCRT-III (Mizuno et al., 2005; Row et al., 2006; Alwan and van Leeuwen, 2007)."
P14_3_3 affects USP8
| 12 39
P14_3_3 binds USP8.
| 11 37
| 11 37

sparser
"In contrast, MS analysis did result in the identification of several serine phosphorylation sites, including the S680 14–3–3 binding site, and subsequent experiments showed that this site is responsib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Using a GST14-3-3 pull-down experiment, we demonstrate here that Usp8 WT and Usp8 640-1080 interact with 14-3-3 proteins."

sparser
"Together, these results indicate that UBPY binds to 14-3-3 proteins via the consensus binding motif around Ser 680 and the binding is regulated by Ser 680 phosphorylation."

sparser
"These mutations inhibited 14-3-3 protein binding to USP8 and resulted in a higher deubiquitinating enzyme (DUB) activation."

sparser
"Therefore, the binding of 14-3-3s to UBPY is possibly a common regulatory mechanism acquired in higher eukaryotes."

sparser
"These results indicated that 14-3-3 proteins bind to the 14-3-3-binding motif around Ser 680 of UBPY when Ser 680 is phosphorylated."

reach
"Indeed, our data demonstrate that Usp8 binds to 14-3-3 proteins in a phosphorylated S680 dependent manner."

reach
"Together, these results indicate that UBPY binds to 14-3-3 proteins via the consensus binding motif around Ser 680 and the binding is regulated by Ser 680 phosphorylation.Previous studies have shown t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Stimulation of cells with EGF does not change the levels of S680 phosphorylation and 14–3–3 binding of Usp8 [35] ."

reach
"Phosphorylation of S680 in the vertebrate conserved amino acid sequence RSYSSP in Usp8 leads to binding of 14-3-3 proteins to Usp8 [34-38]."
P14_3_3 inhibits USP8.
| 1 2
P14_3_3 inhibits USP8. 3 / 5
| 1 2

reach
"Another hypothesis is that USP8 is catalytically inhibited in a phosphorylation dependent manner by 14-3-3 proteins during the interphase stage of the cell-cycle, and this regulation is reversed in the M phase [XREF_BIBR]."

sparser
"Another hypothesis is that USP8 is catalytically inhibited in a phosphorylation-dependent manner by 14-3-3 proteins during the interphase stage of the cell-cycle, and this regulation is reversed in the M phase [ xref ]."

sparser
"We conclude that UBPY is catalytically inhibited in a phosphorylation-dependent manner by 14-3-3s during the interphase, and this regulation is cancelled in the M phase."
SMO affects USP8
| 17 26
SMO binds USP8.
| 15 26
| 15 21

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."

reach
"The finding that USP8 interacted with Smo led to the hypothesis that Hh might control the accessibility of Smo to the DUB."

sparser
"Overall, these results together imply that Rack1 stabilizes Smo and increases Smo cell membrane localization through promoting SmoUsp8 interaction."

reach
"These data suggest that phosphorylation of Smo promotes the formation of a Smo and USP8 complex, which may amplify the Hh stimulation and lead to the activation of Smo."

reach
"However, we found that UBPY decreases Smo ubiquitination regardless of the Hh signaling states and that the association between UBPY and Smo is not significantly affected by either Hh stimulation or Smo phosphorylation, suggesting that Smo deubiquitination by UBPY is unlikely to be a major mechanism by which Hh inhibits Smo ubiquitination, although we can not rule out the possibility that Hh regulates UBPY binding to Smo in a subtle way that escaped the detection by our coimmunoprecipitation assay."

sparser
"Furthermore we show that Hh can enhance the interaction between Smo and USP8."

sparser
"In addition, we found, in an immunoprecipitation experiment, that a substantial amount of Smo SD123 interacted with USP8 ( xref , lane 2, top panel)."

sparser
"We then carried out coimmunoprecipitation assays to determine whether UBPY physically interacts with Smo."

reach
"However, we found that Hrs blocks Smo phosphorylation (XREF_FIG), whereas USP8 does not XREF_BIBR, suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"Intriguingly, with Hh stimulation, Rack1 dissociated from Ci–Cos2 complex and formed a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
SMO binds USP8 and RACK1. 3 / 3
| 3

sparser
"In the presence of Hh, Hh dissociates Ci–Rack1 interaction, and promotes Rack1 forming a trimeric complex with Usp8 and Smo, resulting in Smo deubiquitination and cell surface accumulation (Fig.  xref )."

sparser
"The two-step co-IP assay showed that Usp8, Rack1, and Smo formed a trimeric complex (Fig.  xref )."

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
SMO binds USP8 and HGS. 2 / 2
| 2

sparser
"However, we found that Hrs blocks Smo phosphorylation ( xref ), whereas USP8 does not xref , suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"It is possible that Hrs competes with USP8 for binding Smo, as Hrs and USP8 directly interact with the same domain of Smo."
SMO inhibits USP8.
| 2
SMO inhibits USP8. 2 / 2
| 2

reach
"In contrast, USP8C> S increased Smo ubiquitination, which was similar to the phenotype induced by the RNAi mediated knockdown of USP8 (XREF_FIG, lanes 2 and 4, compare to lane 1, top panel)."

reach
"Hh inhibits Smo ubiquitination by blocking E3 ligase recruitment and promoting Smo deubiquitination through the ubiquitin-specific protease 8 (USP8) in Drosophila ."

reach
"We also observed that down-regulation of USP8 inhibited the proliferation of GC cells which highly expressed HER-3."

reach
"USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K and AKT Signaling Pathway."

sparser
"In conclusion, USP8 inhibitor could inhibit proliferation, abolishes clonogenic ability, and induces apoptosis in pituitary corticotroph tumor cell-AtT20 cells."

reach
"Down-regulation of USP8 Inhibits Cholangiocarcinoma Cell Proliferation and Invasion."

reach
"Both GADD45beta and CABLES1 may be responsible, at least in part, for the USP8 induced suppression of corticotroph tumor cell proliferation."

reach
"Therefore, it was confirmed that down-regulation of USP8 could inhibit the proliferation of NCI-N87, MKN-45 and AGS cell lines, which is HER-3 positive GC cells."

reach
"All in vitro results demonstrated that down-regulation of USP8 inhibited the proliferation and viability of GC cells with high expression of HER3 (NCI-N87, MKN-45 and AGS), but did not affect HER3 negative cells (MGC-803)."

reach
"Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation."

reach
"Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis."

reach
"Moreover, down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle."

reach
"We demonstrated that knockdown of USP8 significantly inhibited the proliferation, migration and invasion of QBC939 and RBE cells in vitro, while USP8 overexpression showed significant promoting effects on Hucct-1 cells."

reach
"Knockdown of USP8 inhibits prostate cancer cell growth, proliferation, and metastasis and promotes docetaxel's activity by suppressing the NF-kB signaling pathway."

reach
"Knockdown of USP8 inhibited the proliferation of human lung cancer cells by regulating cell cycle- and apoptosis-related proteins."

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC

reach
"Our findings indicated that the proliferation, invasion, and stemness of LN229 and T98G cells were markedly suppressed by USP8 inhibition."

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."

reach
"Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis."

reach
"The data showed that knockdown of USP8 inhibited the proliferation and promoted the apoptosis of lung cancer cells."

reach
"In addition, USP8 depletion inhibited the proliferation, invasion and stemness of HCC cells and conferred ferroptosis resistance, which effects could be further rescued by β-catenin overexpression."

reach
"Indeed, inhibition of USP8 either by its knockdown or synthetic small molecule led to attenuation of variety of receptor tyrosine kinase (RTK) activities, resulting in the inhibition of cell proliferation in gefitinib resistant and -sensitive non small cell lung cancer (NSCLC) cells [XREF_BIBR]."
| 7 27 1
| 6 16 1
| 6 16 1

reach
"These results demonstrated that knockdown of USP8 promoted cell apoptosis of lung cancer cells by regulating the PI3K/AKT pathway."

eidos
"USP8 knockdown markedly induced apoptosis and cell cycle arrest ( G 0 / G 1 ) ."

reach
"USP8 knockdown markedly induced apoptosis and cell cycle arrest ( G 0/ G 1)."

reach
"Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2 and Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells."

eidos
"In the present study , our objective is to study in broad the secondary down-stream effect after depleting USP5 or USP8 , which were initially showed to induce apoptosis in various cancers ."

eidos
"DUB-IN-1 , an USP8 inhibitor , caused DNA damage , led to G2 / M phase block by p53-p21 axis , and triggered apoptosis by regulating the p53 target proteins including Bax , Noxa , and Puma ."

eidos
"USP8 inhibitor , DUB-IN-1 , treatment could inhibit esophageal squamous cell carcinoma cell growth and induce G2 / M cell cycle arrest , apoptosis , and autophagy by DNA damage-induced p53 activation ."

reach
"Depletion of USP8 destabilized cFLIP resulting in sensitization to DR-induced apoptosis."

reach
"Knockdown of USP8 inhibited the proliferation of human lung cancer cells by regulating cell cycle- and apoptosis related proteins."

reach
"After transfection with siRNA1 or siRNA2, the expression of Bcl2 was reduced, while the expression of Bax was increased significantly both in A549 and H1299 cells (Figure 4B), indicating that knockdown of USP8 can induce apoptosis of lung cancer cells."
USP8 activates apoptotic process.
| 1 11
| 1 11

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."

reach
"The results indicated that the down-regulation of USP8 could significantly promote the apoptosis of NCI-N87 and MKN-45 cells, but it did not work on MGC-803 cells (XREF_FIG)."

reach
"Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha."

reach
"These results indicated that down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle."

reach
"USP8 silencing significantly inhibits PCa cell growth, survival, and migration and promotes apoptosis by increasing cleaved Caspase 3 and cleaved Caspase 9."

reach
"Knockdown of USP8 inhibited the proliferation of human lung cancer cells by regulating cyclin- and apoptosis-related proteins."

reach
"Knockdown of USP8 inhibited the proliferation of human lung cancer cells by regulating cell cycle- and apoptosis-related proteins."

reach
"Previously, it was reported that knocking down USP8 promotes apoptosis by downregulating FLIP and upregulating cleaved Caspase 3 and cleaved Caspase 8 in HeLa cells (47)."

reach
"Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis."

reach
"In the present study, our objective is to study in broad the secondary down-stream effect after depleting USP5 or USP8, which were initially showed to induce apoptosis in various cancers."
USP8 affects CLEC16A
| 18 13
| 18 10

reach
"Furthermore, we observed that both Nrdp1 stability and ubiquitination were reduced in Min6 β-cells after palmitate treatment (Fig. 6D), thus demonstrating effects consistent with impact on the Clec16a pathway to maintain the upstream mitophagy complex.To determine whether glucolipotoxicity affects Clec16a to impact formation of the Clec16a-Nrdp1-USP8 complex, we overexpressed Clec16a in palmitate-treated Min6 β-cells."

reach
"Further, we observe that diabetogenic metabolic stressors, including elevated glucose and fatty acids, destabilize the CLEC16A, RNF41, and USP8 complex and lead to beta-cell apoptosis."

reach
"Given our findings suggesting that both Nrdp1 stability and ubiquitination regulate formation of the Clec16a-Nrdp1-USP8 complex, we next measured Nrdp1 levels after palmitate treatment in primary islets."

reach
"We next assessed the role of Nrdp1 ubiquitination on formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Previous observations of defective mitochondrial integrity after glucolipotoxicity (7,36), coupled with our findings here of glucolipotoxicity-mediated destabilization of the Clec16a-Nrdp1-USP8 complex, could inspire future in vivo studies to evaluate the importance of dysfunctional mitophagy to β-cell failure in diabetes."

reach
"To determine the importance of maintenance of the Clec16a-Nrdp1-USP8 complex to β-cell survival during glucolipotoxicity, we assessed β-cell apoptosis by cleaved caspase-3 levels after Clec16a overexpression."

sparser
"Given the importance of ubiquitination to Clec16a-Nrdp1-USP8 complex assembly, we hypothesized that specific ubiquitination of Nrdp1 may influence formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Thus, the beta-cell mitophagy pathway requires ubiquitin signals to stabilize the CLEC16A, RNF41, and USP8 complex and maintain mitochondrial quality control."

reach
"While the dynamics of the Clec16a-Nrdp1-USP8 complex are still a mystery, it is clear that Clec16a-mediated ubiquitination orchestrates mitophagic flux in β-cells.Our discovery of Clec16a as an E3 ligase, whose function is inhibited by lenalidomide, expands our insight into its functional role in mitophagy."

sparser
"Furthermore, Clec16a-mediated Nrdp1 ubiquitination is essential for assembly of the Clec16a-Nrdp1-USP8 complex and preservation of β-cell function ( xref )."
| 2

sparser
"However, Clec16a-USP8 binding as well as USP8 levels are reduced after overexpression of the Nrdp1 K-R mutant ( xref )."

sparser
"Interestingly, Clec16a interacts with endogenous USP8, and this interaction is maintained in the presence or absence of Nrdp1 ubiquitin ligase activity ( xref )."

sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."
USP8 affects PRKN
1 | 18 8
USP8 binds PRKN.
| 4 7
| 4 7

reach
"The results showed that NaHS treatment increased the USP8/parkin interaction in db/db cardiac tissues (Fig. 5C)."

sparser
"Our results showed that the effects of exogenous H 2 S on USP8 deubiquitylation and the interaction of USP8 with parkin were blocked with DTT treatment ( xref )."

sparser
"Dithiothreitol, a reducing agent that reverses sulfhydration-mediated covalent modification, increased the ubiquitylation level of parkin, abolished the effects of exogenous H 2 S on USP8 deubiquitylation and suppressed the interaction of USP8 with parkin in neonatal rat cardiomyocytes treated with high glucose, oleate and palmitate."

sparser
"Our results showed that exogenous H 2 S could result in the S-sulfhydration of USP8 under hyperglycemia and hyperlipidemia, leading to the enhanced interaction of USP8 with parkin and the translocation of parkin into mitochondria."

reach
"Our results showed that hyperglycemia and hyperlipidemia decreased the translocation of parkin in the mitochondrial outer membrane and decreased the interaction between USP8 and parkin."

sparser
"Our results showed that hyperglycemia and hyperlipidemia decreased the translocation of parkin in the mitochondrial outer membrane and decreased the interaction between USP8 and parkin."

sparser
"Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in the pathway."

reach
"Our results showed that the S-sulfhydration level of USP8 was obviously decreased in vivo and in vitro under hyperglycemia and hyperlipidemia, however, exogenous H 2 S could reverse this effect and promote USP8/parkin interaction."

sparser
"Further, DTT inhibited the interaction of USP8 with parkin."

sparser
"In the diabetic heart, ubiquitin specific peptidase 8 (USP8) has been implicated: H 2 S was found to increase the association of parkin with USP8."
USP8 activates PRKN.
| 7
USP8 activates PRKN. 7 / 8
| 7

reach
"USP8 KD also prevented Parkin KO DA neurons loss and normalized mitochondrial morphological defects, although it did not ameliorate Parkin climbing performance (XREF_FIG)."

reach
"H 2 S may upregulate the expression of deubiquitinating enzymes USP8 to antagonize the degradation of Parkin protein."

reach
"In contrast, USP8 promotes parkin mediated mitophagy and thus agonists of this DUB could be developed XREF_BIBR."

reach
"USP8 Down-Regulation Promotes Parkin-Independent Mitophagy in the Drosophila Brain and in Human Neurons."

reach
"The E3 ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp1) and the deubiquitination enzyme ubiquitin-specific protease 8 (USP8) counterbalance ubiquitin dynamics to direct Parkin action or its proteasomal degradation (10,11)."

reach
"Only USP8 supports mitophagy by stabilizing the E3 ligase Parkin."

reach
"In contrast, USP8 promotes Parkin mediated mitophagy and agonists to USP8 could be developed as potential therapeutics."
USP8 deubiquitinates PRKN.
1 | 6
USP8 deubiquitinates PRKN. 7 / 7
1 | 6

reach
"At present, the negative regulatory mechanisms against Parkin-mediated ubiquitination have been reported, with the discovery of several deubiquitinases including USP8, USP15 and USP30 that are able to cause the deubiquitination of Parkin and/or OMM proteins."

reach
"Our findings suggested that H 2 S promoted mitophagy formation by increasing S sulfhydration of USP8, which enhanced deubiquitination of parkin through the recruitment of parkin in mitochondria."

reach
"This process is negatively regulated by USP15 [XREF_BIBR] and USP30 [XREF_BIBR], which deubiquitinate mitochondrial Parkin-targets, while it is supported by USP8, which deubiquitinates Parkin itself [XREF_BIBR]."

reach
"Whilst the phosphatase that dephosphorylates p-Ub remains unknown, two DUBs have been identified that deubiquitylate Parkin directed substrates, USP30 and USP15, and USP8 has also been reported to reverse Parkin autoubiquitylation."

"USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin."

reach
"Finally, deubiquitination of Parkin by USP8 is required for Parkin recruitment to CCCP intoxicated mitochondria and to promote stress induced mitophagy in vitro."

reach
"USP8 deubiquitylation of auto-ubiquitylated Parkin is required for its localization to depolarized mitochondria, and thereby for efficient activation of mitophagy [XREF_BIBR]."
USP8 ubiquitinates PRKN.
| 1 1
USP8 leads to the ubiquitination of PRKN. 2 / 2
| 1 1

sparser
"Utilizing a mutant ubiquitin only capable of K6-linked conjugates, we observed the expected reduction of K6-linked Parkin ubiquitination by USP8 ( xref )."

reach
"USP8, instead, antagonizes mitophagy by directly deubiquitinating PARKIN, so contributing to its recruitment and activity."
RNF41 affects CLEC16A
| 18 11
| 18 10

reach
"Furthermore, we observed that both Nrdp1 stability and ubiquitination were reduced in Min6 β-cells after palmitate treatment (Fig. 6D), thus demonstrating effects consistent with impact on the Clec16a pathway to maintain the upstream mitophagy complex.To determine whether glucolipotoxicity affects Clec16a to impact formation of the Clec16a-Nrdp1-USP8 complex, we overexpressed Clec16a in palmitate-treated Min6 β-cells."

reach
"Further, we observe that diabetogenic metabolic stressors, including elevated glucose and fatty acids, destabilize the CLEC16A, RNF41, and USP8 complex and lead to beta-cell apoptosis."

reach
"Given our findings suggesting that both Nrdp1 stability and ubiquitination regulate formation of the Clec16a-Nrdp1-USP8 complex, we next measured Nrdp1 levels after palmitate treatment in primary islets."

reach
"We next assessed the role of Nrdp1 ubiquitination on formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Previous observations of defective mitochondrial integrity after glucolipotoxicity (7,36), coupled with our findings here of glucolipotoxicity-mediated destabilization of the Clec16a-Nrdp1-USP8 complex, could inspire future in vivo studies to evaluate the importance of dysfunctional mitophagy to β-cell failure in diabetes."

reach
"To determine the importance of maintenance of the Clec16a-Nrdp1-USP8 complex to β-cell survival during glucolipotoxicity, we assessed β-cell apoptosis by cleaved caspase-3 levels after Clec16a overexpression."

sparser
"Given the importance of ubiquitination to Clec16a-Nrdp1-USP8 complex assembly, we hypothesized that specific ubiquitination of Nrdp1 may influence formation of the Clec16a-Nrdp1-USP8 complex."

reach
"Thus, the beta-cell mitophagy pathway requires ubiquitin signals to stabilize the CLEC16A, RNF41, and USP8 complex and maintain mitochondrial quality control."

reach
"While the dynamics of the Clec16a-Nrdp1-USP8 complex are still a mystery, it is clear that Clec16a-mediated ubiquitination orchestrates mitophagic flux in β-cells.Our discovery of Clec16a as an E3 ligase, whose function is inhibited by lenalidomide, expands our insight into its functional role in mitophagy."

sparser
"Furthermore, Clec16a-mediated Nrdp1 ubiquitination is essential for assembly of the Clec16a-Nrdp1-USP8 complex and preservation of β-cell function ( xref )."

sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."
USP8 affects STAM
4 1 1 | 9 10
USP8 binds STAM.
4 1 | 6 10
4 1 | 5 3

No evidence text available

reach
"Hrs is constitutively associated with STAM, which in turn can bind to the deubiquitinating enzyme UBPY [38], implying that the correlation between E3 ligase POSH and UBPY (or unidentified DUB) might m[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

sparser
"Hrs is constitutively associated with STAM, which in turn can bind to the deubiquitinating enzyme UBPY [38] , implying that the correlation between E3 ligase POSH and UBPY (or unidentified DUB) might[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In contrast, stability of the UBPY binding partner STAM is dramatically compromised in UBPY knockdown cells."

No evidence text available

No evidence text available

sparser
"It has been shown previously that a subset of SH3 domains bind ubiquitin ( xref , xref ), and a recent study using NMR titration experiments showed that the SH3 domain of STAM does in fact bind ubiquitin, and that this interaction can be competed off by USP8 binding to the SH3 domain of STAM ( xref )."

reach
"USP8 can form complexes with the ESCRT-0 subunit STAM on endosomes, stimulating de-ubiquitination of EGFR on endosomes, and promoting EGFR endosome-to-plasma membrane recycling [XREF_BIBR]."

reach
"Both AMSH and Usp8 bind to ESCRT-0 protein STAM through a non canonical SH3 binding motif, and with their MIT-domain to several CHMP proteins of the ESCRT-III machinery [30,37,39,40]."
STAM binds USP8 and STAMBP. 5 / 5
| 5

sparser
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner ( xref )."

sparser
"The functional relevance of the interaction between USP8, AMSH, and STAM in the endocytic trafficking of activated growth factors is supported by other observations, including that catalytically inactive AMSH, a potential “substrate trap” mutant, resulted in the accumulation of ubiquitin on endosomes, an increased association with STAM, and the generation of a minor product consistent with ubiquitylated STAM ( xref )."

sparser
"This also contains the sequence PPPRPTAPKP, which binds the Mona SH3 domain [ 39 ] and closely resembles the PXXXRXXKP motifs in UBPY [ 21, 28 ] and AMSH [ 20 ] that bind STAM SH3."

sparser
"AMSH (a JAMM family member with specificity for K63 chains) and USP8 associate with STAM proteins, a component of the ESCRT-0 complex xref , xref ."

sparser
"Both AMSH and Usp8 bind to ESCRT-0 protein STAM through a non-canonical SH3-binding motif, and with their MIT-domain to several CHMP proteins of the ESCRT-III machinery [30,37,39,40] ."
STAM binds USP8, STAMBP, and HRS. 1 / 1
| 1

sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
STAM binds USP8 and SH3 domain. 1 / 1
| 1

reach
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner."
USP8 deubiquitinates STAM.
1 | 3
USP8 deubiquitinates STAM. 4 / 4
1 | 3

reach
"USP8 modulates EGFR trafficking by regulating STAM de-ubiquitination on early endosomes 11."

reach
"In addition, we identified STAM and NFX1, which are known to be deubiquitylated by USP8 and USP9 respectively."

reach
"USP8 deubiquitinates STAM, preventing its degradation by the proteasome [XREF_BIBR], and Nrdp1, an E3 required for the lysosomal degradation of EGFR family members ErbB3 and ErbB4 [XREF_BIBR]."

"UBPY function is essential for effective downregulation but is likely to be multifaceted, encompassing activity against both K63-linked and K48-linked polyubiquitin chains and including regulation of the stability of ESCRT-associated proteins such as STAM, by reversing their ubiquitination."
1 1 | 9 12
USP8 translocates.
| 9 12
USP8 translocates to the membrane. 10 / 13
| 5 8

sparser
"Nevertheless, our findings demonstrate that optimal Usp8 tyrosine phosphorylation requires an intact Usp8 MIT domain, which is consistent with the proposed role of the MIT domain in recruitment of Usp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Our findings are most consistent with the model that MIT domain dependent recruitment of Usp8 to endosomal membranes is important for low stoichiometry SRC mediated tyrosine phosphorylation of multiple Usp8 tyrosines."

sparser
"The MIT domain in Usp8 was first identified by Row and coworkers, who showed that the MIT domain interacts with Escrt-III CHMP proteins and is necessary for the recruitment of Usp8 to endosomal membra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Our findings are most consistent with the model that MIT domain-dependent recruitment of Usp8 to endosomal membranes is important for low stoichiometry SRC-mediated tyrosine phosphorylation of multiple Usp8 tyrosines."

sparser
"These findings are consistent with the model that Usp8 is tyrosine phosphorylated upon MIT-dependent recruitment of Usp8 to endosomal membranes [17,21] ."

reach
"These findings are consistent with the model that Usp8 is tyrosine phosphorylated upon MIT dependent recruitment of Usp8 to endosomal membranes [17,21]."

reach
"Interestingly, removal of the MIT domain does not completely abolish Usp8 tyrosine phosphorylation, suggesting that Usp8 might be recruited to endosomal membranes also via alternative mechanisms (e.g.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"5 and 6 ), suggesting that Usp8 might also be recruited to endosomal membranes through alternative mechanisms."

reach
"Nevertheless, our findings demonstrate that optimal Usp8 tyrosine phosphorylation requires an intact Usp8 MIT domain, which is consistent with the proposed role of the MIT domain in recruitment of Usp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Interestingly, removal of the MIT domain does not completely abolish Usp8 tyrosine phosphorylation, suggesting that Usp8 might be recruited to endosomal membranes also via alternative mechanisms (e.g.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 translocates to the endosome. 7 / 7
| 4 3

reach
"We focused on the N-terminal MIT domain of UBPY, which also binds CHMP4B, because this is essential for recruiting UBPY to endosomes and supporting EGFR degradation [19]."

reach
"USP8 is recruited to endosomes upon EGF stimulation but shows no association with endosomes in starved cells in contrast to AMSH."

reach
"On the other hand, human USP8 recruitment to the endosomes is dependent on its N-terminal MIT (microtubule interacting and transport) domain that associates with components of the ESCRT XREF_BIBR."

sparser
"Given that ErbB receptors are present on endosomal membranes, we hypothesized that MIT-dependent endosomal recruitment of Usp8 is required for Usp8 tyrosine phosporylation."

sparser
"USP8 is recruited to endosomes upon EGF stimulation but shows no association with endosomes in starved cells in contrast to AMSH ( xref )."

sparser
"We investigated in more detail how UBPY bound HD-PTP Bro1-V. We focused on the N-terminal MIT domain of UBPY, which also binds CHMP4B, because this is essential for recruiting UBPY to endosomes and su[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Finally, USP8 and AMSH (associated molecule with the SH3 domain of STAM), two DUBs that are usually recruited to endosomes, have an important role in cytokinesis."
USP8 translocates from the cytoplasm. 1 / 1
| 1

sparser
"We speculate that only a relatively small fraction of cellular Usp8 is recruited from the cytoplasm towards endosomes, resulting in a low stoichiometry of tyrosine phosphorylated Usp8."
USP8 binds.
1 1 |
1 1 |

No evidence text available

No evidence text available
USP8 affects EPG5
1 | 14 8
USP8 deubiquitinates EPG5.
1 | 11
USP8 deubiquitinates EPG5. 10 / 12
1 | 11

reach
"When we overexpressed Usp8 in ESCs, the ubiquitin modification of EPG5 decreased, while reduced Usp8 expression increased EPG5 ubiquitination (Fig. 5a, b)."

reach
"USP8 regulates ESC identity through deubiquitinating EPG5."

"Mechanistically, USP8 directly removes non-classical K63-linked ubiquitin chains from EPG5 at Lysine 252, leading to enhanced interaction between EPG5 and LC3."

reach
"We revealed that the deubiquitinase USP8 maintains ESC identity by directly deubiquitinating EPG5 to consolidate the interaction between EPG5 and LC3 and sustain the normal autophagic flux for stemness maintenance (Fig. 6g)."

reach
"These data suggested EPG5 is degraded through autophagy in ESCs.In conclusion, we defined a novel mechanism, involving USP8 deubiquitination of EPG5, which underlies autophagy regulation in ESCs."

reach
"To test whether USP8 deubiquitinates EPG5, we examined the ubiquitination levels in either Usp8-overexpression or Usp8 ESCs."

reach
"USP8 maintains embryonic stem cell stemness via deubiquitination of EPG5."

reach
"Since USP8 directly deubiquitinates EPG5 at K252, we next investigated whether deubiquitination of EPG5 by USP8 impairs the interactions between EPG5 and LC3 and eventually affects ESC stemness."

reach
"We propose that deubiquitination of EPG5 by USP8 guards the autophagic flux in ESCs to maintain their stemness."

reach
"USP8 deubiquitinates EPG5 by removing K63-ubiquitin chains."
USP8 binds EPG5.
| 3 8
| 3 8

reach
"The results showed that USP8 is immunoprecipitated by EPG5, indicating that there is an interaction between EPG5 and USP8 (Fig. 3b)."

sparser
"Co-IP assay confirmed the interaction between EPG5 and USP8 in ESCs (Fig.  xref )."

sparser
"Furthermore, immunofluorescence microscopy showed that EPG5 did directly interact with USP8 in ESCs (Fig.  xref )."

sparser
"The results showed that USP8 is immunoprecipitated by EPG5, indicating that there is an interaction between EPG5 and USP8 (Fig.  xref )."

sparser
"These data support that EPG5 binds to USP8."

reach
"These data support that EPG5 binds to USP8."

reach
"To examine whether USP8 binds to EPG5 in cells, we transfected Flag-tagged Epg5 and/or HA-tagged Usp8 in HEK293T cells and performed coimmunoprecipitation (co-IP) assays."

sparser
"To examine whether USP8 binds to EPG5 in cells, we transfected Flag-tagged Epg5 and/or HA-tagged Usp8 in HEK293T cells and performed coimmunoprecipitation (co-IP) assays."

sparser
"EPG5 directly interacts with USP8."

sparser
"To further confirm that EPG5 interacts with USP8 in ESCs, stable ESC lines harboring HA- Epg5 or Myc- Usp8 vectors were established."
STAM affects USP8
4 1 | 6 10
4 1 | 5 3

No evidence text available

reach
"Hrs is constitutively associated with STAM, which in turn can bind to the deubiquitinating enzyme UBPY [38], implying that the correlation between E3 ligase POSH and UBPY (or unidentified DUB) might m[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

sparser
"Hrs is constitutively associated with STAM, which in turn can bind to the deubiquitinating enzyme UBPY [38] , implying that the correlation between E3 ligase POSH and UBPY (or unidentified DUB) might[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In contrast, stability of the UBPY binding partner STAM is dramatically compromised in UBPY knockdown cells."

No evidence text available

No evidence text available

sparser
"It has been shown previously that a subset of SH3 domains bind ubiquitin ( xref , xref ), and a recent study using NMR titration experiments showed that the SH3 domain of STAM does in fact bind ubiquitin, and that this interaction can be competed off by USP8 binding to the SH3 domain of STAM ( xref )."

reach
"USP8 can form complexes with the ESCRT-0 subunit STAM on endosomes, stimulating de-ubiquitination of EGFR on endosomes, and promoting EGFR endosome-to-plasma membrane recycling [XREF_BIBR]."

reach
"Both AMSH and Usp8 bind to ESCRT-0 protein STAM through a non canonical SH3 binding motif, and with their MIT-domain to several CHMP proteins of the ESCRT-III machinery [30,37,39,40]."
STAM binds USP8 and STAMBP. 5 / 5
| 5

sparser
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner ( xref )."

sparser
"The functional relevance of the interaction between USP8, AMSH, and STAM in the endocytic trafficking of activated growth factors is supported by other observations, including that catalytically inactive AMSH, a potential “substrate trap” mutant, resulted in the accumulation of ubiquitin on endosomes, an increased association with STAM, and the generation of a minor product consistent with ubiquitylated STAM ( xref )."

sparser
"This also contains the sequence PPPRPTAPKP, which binds the Mona SH3 domain [ 39 ] and closely resembles the PXXXRXXKP motifs in UBPY [ 21, 28 ] and AMSH [ 20 ] that bind STAM SH3."

sparser
"AMSH (a JAMM family member with specificity for K63 chains) and USP8 associate with STAM proteins, a component of the ESCRT-0 complex xref , xref ."

sparser
"Both AMSH and Usp8 bind to ESCRT-0 protein STAM through a non-canonical SH3-binding motif, and with their MIT-domain to several CHMP proteins of the ESCRT-III machinery [30,37,39,40] ."
STAM binds USP8, STAMBP, and HRS. 1 / 1
| 1

sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
STAM binds USP8 and SH3 domain. 1 / 1
| 1

reach
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner."
BIRC6 affects USP8
4 1 | 8 9
BIRC6 binds USP8.
4 1 | 7 8
4 1 | 1 2

reach
"USP8 interactions with Nrdp1 and BRUCE."

sparser
"Importantly, interactions of USP8 and BRUCE in the nucleus not only define a role of USP8 in the DNA damage response but may also point to a role in cytokinesis which would be in line with its profound role in regulation of the ESCRT machinery [ xref ]."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"These include the interaction of USP8 with BRUCE in the regulation of DSB repair."

No evidence text available
USP8 binds BIRC6 and BRIT1. 6 / 6
| 6

reach
"Given the fact that the integrity of the BRUCE, USP8, and BRIT1 complex is essential for targeting BRIT1 to DSB, whether the observed UBC requirement is attributable to its contribution to maintaining the complex integrity was examined."

reach
"Mutation or deletion of the BRUCE UBC domain did not disrupt the BRUCE, USP8, and BRIT1 complex, but impaired deubiquitination and consequent recruitment of BRIT1 to DSB."

reach
"Once deubiquitinated, BRIT1 is released from the BRUCE, USP8, and BRIT1 complex and targeted to DSBs by binding to gamma-H2AX at sites of DSB [XREF_BIBR], where BRIT1 recruits the SWI/SNF chromatin remodeling complex to facilitate relaxation of chromatin configuration for the access of repair factors to damaged chromatin [XREF_BIBR]."

reach
"The formation of the BRUCE, USP8, and BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

reach
"This deubiquitination triggers the release of BRIT1 from the BRUCE, USP8, and BRIT1 complex and consequently released BRIT acquires the ability to be recruited to sites of DNA damage by binding to phosphorylated H2AX (gamma-H2AX)."

reach
"Together, these results indicate that subsequent to the formation of the BRUCE, USP8, and BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
USP8 binds BIRC6 and MCPH1. 5 / 5
| 5

sparser
"Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex."

sparser
"Specifically, the BIR is dispensible for the scaffold function of BRUCE in tethering USP8 and BRIT1 forming the nuclear BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"The formation of the BRUCE-USP8-BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

sparser
"In the recently elucidated role of BRUCE in the regulation of DNA damage signaling and repair, neither the BIR or UBC is required for the scaffold function of BRUCE in the formation of BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"Together, these results indicate that subsequent to the formation of the BRUCE-USP8-BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
USP8 binds BIRC6 and RNF41. 1 / 1
| 1

sparser
"USP8 interactions with Nrdp1 and BRUCE."
BIRC6 ubiquitinates USP8.
| 1 1
BIRC6 ubiquitinates USP8. 2 / 2
| 1 1

sparser
"The putative substrate of BRUCE could be USP8 and if this is the case, ubiquitination of USP8 by BRUCE is expected to enhance its Dub activity over Ub-BRIT1, thereby facilitating removal of the Ub chains from K63-Ub-BRIT1 and promoting recruitment of de-ubiquitinated BRIT1 to sites of DNA damage."

reach
"The putative substrate of BRUCE could be USP8 and if this is the case, ubiquitination of USP8 by BRUCE is expected to enhance its Dub activity over Ub-BRIT1, thereby facilitating removal of the Ub chains from K63-Ub-BRIT1 and promoting recruitment of de-ubiquitinated BRIT1 to sites of DNA damage."
USP8 affects BIRC6
4 1 | 8 8
USP8 binds BIRC6.
4 1 | 7 8
4 1 | 1 2

reach
"USP8 interactions with Nrdp1 and BRUCE."

sparser
"Importantly, interactions of USP8 and BRUCE in the nucleus not only define a role of USP8 in the DNA damage response but may also point to a role in cytokinesis which would be in line with its profound role in regulation of the ESCRT machinery [ xref ]."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"These include the interaction of USP8 with BRUCE in the regulation of DSB repair."

No evidence text available
USP8 binds BIRC6 and BRIT1. 6 / 6
| 6

reach
"Given the fact that the integrity of the BRUCE, USP8, and BRIT1 complex is essential for targeting BRIT1 to DSB, whether the observed UBC requirement is attributable to its contribution to maintaining the complex integrity was examined."

reach
"Mutation or deletion of the BRUCE UBC domain did not disrupt the BRUCE, USP8, and BRIT1 complex, but impaired deubiquitination and consequent recruitment of BRIT1 to DSB."

reach
"Once deubiquitinated, BRIT1 is released from the BRUCE, USP8, and BRIT1 complex and targeted to DSBs by binding to gamma-H2AX at sites of DSB [XREF_BIBR], where BRIT1 recruits the SWI/SNF chromatin remodeling complex to facilitate relaxation of chromatin configuration for the access of repair factors to damaged chromatin [XREF_BIBR]."

reach
"The formation of the BRUCE, USP8, and BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

reach
"This deubiquitination triggers the release of BRIT1 from the BRUCE, USP8, and BRIT1 complex and consequently released BRIT acquires the ability to be recruited to sites of DNA damage by binding to phosphorylated H2AX (gamma-H2AX)."

reach
"Together, these results indicate that subsequent to the formation of the BRUCE, USP8, and BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
USP8 binds BIRC6 and MCPH1. 5 / 5
| 5

sparser
"Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex."

sparser
"Specifically, the BIR is dispensible for the scaffold function of BRUCE in tethering USP8 and BRIT1 forming the nuclear BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"The formation of the BRUCE-USP8-BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

sparser
"In the recently elucidated role of BRUCE in the regulation of DNA damage signaling and repair, neither the BIR or UBC is required for the scaffold function of BRUCE in the formation of BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"Together, these results indicate that subsequent to the formation of the BRUCE-USP8-BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
USP8 binds BIRC6 and RNF41. 1 / 1
| 1

sparser
"USP8 interactions with Nrdp1 and BRUCE."
USP8 inhibits BIRC6.
| 1
USP8 inhibits BIRC6. 1 / 1
| 1

reach
"Dex also elevated the deubiquitinating enzyme, Usp8 and Ubpy, which via Nrdp1 decreases BRUCE."
USP8 affects STAM2
5 2 | 8 3
USP8 binds STAM2.
5 2 | 4 3
5 2 | 4 3

No evidence text available

reach
"Finally, STAM2 interaction with USP8 facilitates deubiquitination of the EGFR leading to its dissociation from ESCRT-0 and engagement with ESCRT-III."

No evidence text available

sparser
"Finally, STAM2 interaction with USP8 facilitates deubiquitination of the EGFR leading to its dissociation from ESCRT-0 and engagement with ESCRT-III."

No evidence text available

reach
"In addition, C-terminal portion of this P3 sequence is needed for effective binding to SH3 as in the study by Kato et al. [12], since P2 containing the N-terminal five residues of the novel sequence c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Competitive binding of UBPY and ubiquitin to the STAM2 SH3 domain revealed by NMR."

sparser
"Gab2b exhibits the canonical RxxK motif and adopts a relatively extended conformation on the surface of Grb2SH3C much in the fashion of SLP-76 and HPK1 binding to Mona/Gads SH3C ( Figures 4 A–4D) ( Ha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

No evidence text available
USP8 decreases the amount of STAM2.
| 2
USP8 decreases the amount of STAM2. 2 / 2
| 2

reach
"siRNAs USP8 (B) and (C) reduced expression of MET and STAM2."

reach
"UBPy deficient cells exhibit aberrantly enlarged early endosomes colocalizing with enhanced ubiquitination and have reduced levels of HRS and STAM2."
USP8 activates STAM2.
| 2
USP8 activates STAM2. 2 / 2
| 2

reach
"Hence, locally recruited UBPY might aid the displacement of STAM2 from HD-PTP."

reach
"These binding reactions provide a scenario in which UBPY could aid transit of EGFR to ESCRT-III by helping to displace STAM2 from HD-PTP."
USP8 affects LRIG1
1 1 | 13 5
USP8 binds LRIG1.
1 | 5 5
1 | 5 5

reach
"Collectively, these results suggest that SAIT301 triggers degradation of LRIG1 by interfering the interaction of USP8 and LRIG1, and USP8 regulates ubiquitin modification and stability of LRIG1."

reach
"Interestingly, SAIT301 treatment markedly decreased the interaction of LRIG1 and USP8 (XREF_FIG)."

sparser
"Interestingly, SAIT301 triggers LRIG1/Met degradation by interfering with LRIG1-USP8 interaction."

reach
"SAIT301 triggers degradation of LRIG1 by inhibiting the interaction of LRIG1 and USP8, which regulates ubiquitin modification and stability of LRIG1."

sparser
"We also identified USP8 as a LRIG1-specific deubiquitinating enzyme, reporting the interaction between USP8 and LRIG1 for the first time."

sparser
"Collectively, these results suggest that SAIT301 triggers degradation of LRIG1 by interfering the interaction of USP8 and LRIG1, and USP8 regulates ubiquitin modification and stability of LRIG1."

sparser
"We demonstrated that SAIT301 inhibits the interaction of LRIG1 and USP8."

reach
"We also identified USP8 as a LRIG1 specific deubiquitinating enzyme, reporting the interaction between USP8 and LRIG1 for the first time."

sparser
"Interestingly, SAIT301 treatment markedly decreased the interaction of LRIG1 and USP8 ( xref )."

No evidence text available
USP8 deubiquitinates LRIG1.
1 | 3
USP8 deubiquitinates LRIG1. 3 / 3
1 | 2

reach
"To determine whether endogenous USP8 deubiquitinates LRIG1, we used shUSP8 to decrease the level of endogenous USP8 in EBC1 cells."

reach
"Also, when over-expressed, USP8 decreases LRIG1 ubiquitination by SAIT301 treatment (XREF_FIG)."
Modified USP8 leads to the deubiquitination of LRIG1. 1 / 1
| 1

reach
"SAIT301 treatment significantly enhanced the ubiquitination of LRIG1, whereas over-expression of USP8 markedly diminished the ubiquitination of LRIG1 (XREF_FIG)."
USP8 activates LRIG1.
| 4
USP8 activates LRIG1. 4 / 4
| 4

reach
"These results suggest that simultaneous blockage of USP8 may further enhance LRIG1 dependent Met degradation and subsequent tumor growth inhibition by SAIT301 and other Met targeting drugs that have a similar mechanism of action."

reach
"This result suggests that SAIT301 perturbs USP8 mediated modulation of LRIG1, resulting in the degradation of LRIG1."

reach
"Over-expression of USP8 substantially reduced the LRIG1 degradation (XREF_FIG)."

reach
"Moreover, we showed that suppression of USP8 activity, by over-expression of USP8-CS, led to enhancement of the anti-tumor activity of Met targeting therapeutic antibody by promoting degradation of both Met and LRIG1."
USP8 ubiquitinates LRIG1.
| 1
USP8 ubiquitinates LRIG1. 1 / 1
| 1

reach
"Ubiquitinated LRIG1 recruits c-Met to lysosomes for degradation; reduction in LRIG1 ubiquitination by USP8 depletion or inactivation thus enables c-Met levels and functionality to be maintained."
USP8 affects CHMP1B
4 1 | 8 7
USP8 binds CHMP1B.
4 | 1 6
4 | 1 6

sparser
"Eleven confirmed hits inhibited the USP8::CHMP1B interaction within a range of 30% to 70% inhibition at 50 µM, while they were inactive on a set of other PPI interfaces demonstrating the feasibility of specifically disrupting this particular interface."

No evidence text available

sparser
"As anticipated from earlier studies, a deletion of the MIM (Microtubule Interacting and Trafficking domain Interacting Motif) domain or mutation of two conserved leucine residues, L192 and L195, in this domain respectively abolished or strongly impeded the USP8::CHMP1B interaction."

sparser
"The USP8 MIT domain binds tightly to CHMP1B and more weakly to a subset of other CHMPs ( xref )."

sparser
"Interaction of CHMP1B with USP8 occurs via α-helices 4, 5, and 6 of CHMP1B."

No evidence text available

No evidence text available

No evidence text available

reach
"Full-length CHMP1B and alpha-helices 4, 5 and 6 interacted with Flag-USP8 in this assay (XREF_FIG)."

sparser
"The function of USP8 at the endocytic pathway level partly relies on binding to and deubiquitination of the Endosomal Sorting Complex Required for Transport (ESCRT) protein CHMP1B. In the aim of finding chemical inhibitors of the USP8::CHMP1B interaction, we performed a high-throughput screening campaign using an HTRF® assay to monitor the interaction directly in lysates of cells co-expressing both partners."
USP8 deubiquitinates CHMP1B.
1 | 6
USP8 deubiquitinates CHMP1B. 7 / 7
1 | 6

reach
"Furthermore, we have demonstrated that USP8 deubiquitinates CHMP1B."

reach
"Based on these observations, we propose that CHMP1B is dynamically regulated by ubiquitination in response to EGF and that USP8 triggers CHMP1B deubiquitination possibly favoring its subsequent assembly into a membrane associated ESCRT-III polymer."

reach
"Finally, we observed that the ubiquitination level of endogenous CHMP1B was higher in partially Usp8 silenced cells compared to control cells, strengthening the hypothesis that USP8 deubiquitinates CHMP1B (XREF_FIG)."

reach
"Thus, deubiquitination of CHMP1B by USP8 at the endosomal membrane may favor CHMP1B oligomerization and co-assembly with IST1 in vivo."

reach
"From these observations, we propose that CHMP1B is dynamically regulated by ubiquitination in response to EGF and that USP8 triggers CHMP1B deubiquitination possibly favoring its subsequent assembly into a membrane associated ESCRT-III polymer."

"We demonstrate further that CHMP1B is deubiquitinated by the ubiquitin specific protease USP8 (syn. UBPY)"

reach
"Our results thus strongly suggest that USP8 deubiquitinates CHMP1B."
USP8 ubiquitinates CHMP1B.
| 1 1
USP8 leads to the ubiquitination of CHMP1B. 2 / 2
| 1 1

reach
"Others suggest that USP8 counter-regulates EGF-induced ubiquitination of the ESCRT-III component CHMP1B, allowing it to assemble into a membrane-associated ESCRT-III polymer required for budding [34]."

sparser
"Others suggest that USP8 counter-regulates EGF-induced ubiquitination of the ESCRT-III component CHMP1B, allowing it to assemble into a membrane-associated ESCRT-III polymer required for budding [ xref ]."
STAM2 affects USP8
5 2 | 5 3
STAM2 binds USP8.
5 2 | 4 3
5 2 | 4 3

No evidence text available

reach
"Finally, STAM2 interaction with USP8 facilitates deubiquitination of the EGFR leading to its dissociation from ESCRT-0 and engagement with ESCRT-III."

No evidence text available

sparser
"Finally, STAM2 interaction with USP8 facilitates deubiquitination of the EGFR leading to its dissociation from ESCRT-0 and engagement with ESCRT-III."

No evidence text available

reach
"In addition, C-terminal portion of this P3 sequence is needed for effective binding to SH3 as in the study by Kato et al. [12], since P2 containing the N-terminal five residues of the novel sequence c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Competitive binding of UBPY and ubiquitin to the STAM2 SH3 domain revealed by NMR."

sparser
"Gab2b exhibits the canonical RxxK motif and adopts a relatively extended conformation on the surface of Grb2SH3C much in the fashion of SLP-76 and HPK1 binding to Mona/Gads SH3C ( Figures 4 A–4D) ( Ha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

No evidence text available
STAM2 activates USP8.
| 1
STAM2 activates USP8. 1 / 1
| 1

reach
"Reduced MET, EGFR, and STAM2 expression was consistent with attenuation of USP8 at DUBs-IN-3 concentrations that selectively increased death in cSCC cells (XREF_FIG d)."
USP8 affects STAMBP
| 2 14
| 2 5

sparser
"Both AMSH and Usp8 bind components of the endosomal sorting complex for transport (ESCRT) which are involved in targeting ubiquitinated cargo receptors for incorporation into intraluminal vesicles (IL[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The interaction of the two endosomal DUBs, AMSH, and USP8 (UBPY in yeast), with a UIM-containing signal transducing adaptor molecule 2 (STAM2) enhances their deubiquitinating efficacy via substrate arrest [ xref , xref ]."

reach
"The DUBs AMSH (associated molecule with the SH3 domain of STAM) XREF_BIBR and UBPY (ubiquitin isopeptidase Y/ubiquitin specific protease 8) XREF_BIBR, bind both the ESCRT-0 component STAM (signal transducing adaptor molecule) and ESCRT and III complex members XREF_BIBR, and are implicated in regulating EGFR sorting onto the degradative pathway."

sparser
"AMSH and USP8 can also interact with CHMP proteins that are components of the late ESCRT-III machinery xref , xref ."

reach
"The competitive binding of AMSH and USP8 to ESCRT subunits, and the fact that they associate with both ESCRT-0 and -III, suggests that these DUBs may regulate cargo deubiquitination in complex ways."

sparser
"AMSH and Usp8 bind with their PxxP motif to the non-canonical SH3-binding motif of ESCRT-0 protein STAM, and with their MIT (Microtubule Interacting and Transport)-domain to several CHMP proteins of t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The competitive binding of AMSH and USP8 to ESCRT subunits, and the fact that they associate with both ESCRT-0 and –III, suggests that these DUBs may regulate cargo deubiquitination in complex ways."
STAM binds USP8 and STAMBP. 5 / 5
| 5

sparser
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner ( xref )."

sparser
"The functional relevance of the interaction between USP8, AMSH, and STAM in the endocytic trafficking of activated growth factors is supported by other observations, including that catalytically inactive AMSH, a potential “substrate trap” mutant, resulted in the accumulation of ubiquitin on endosomes, an increased association with STAM, and the generation of a minor product consistent with ubiquitylated STAM ( xref )."

sparser
"This also contains the sequence PPPRPTAPKP, which binds the Mona SH3 domain [ 39 ] and closely resembles the PXXXRXXKP motifs in UBPY [ 21, 28 ] and AMSH [ 20 ] that bind STAM SH3."

sparser
"AMSH (a JAMM family member with specificity for K63 chains) and USP8 associate with STAM proteins, a component of the ESCRT-0 complex xref , xref ."

sparser
"Both AMSH and Usp8 bind to ESCRT-0 protein STAM through a non-canonical SH3-binding motif, and with their MIT-domain to several CHMP proteins of the ESCRT-III machinery [30,37,39,40] ."
STAM binds USP8, STAMBP, and HRS. 1 / 1
| 1

sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
USP8 binds STAMBP and AVP. 1 / 1
| 1

sparser
"Like Doa4 in yeast, mammalian Usp8 and AMSH associate with class E Vps proteins on endosomes."
| 1

sparser
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
| 2 13
| 2 11

reach
"Overexpression of USP8 promotes PCa cell migration and diminished docetaxel activity."

reach
"It also shows that USP8 overexpression suppresses docetaxel’s activity, thereby increasing EGFR and PI3K-mediated NF-kB signal activation."

reach
"Its overexpression increased the PCa cell migration and diminished the healing action of docetaxel in both cells.Similar to the wound healing assay, overexpression of USP8 resulted in the highest number of migrated cells for both Du145 and PC3 cells in the Transwell assay, which showed statistical significance compared to all other treatment group cells ( Figure 3B )."

eidos
"Our findings revealed that USP8 plays an oncogenic role in PCa and can suppress docetaxel activity ."

eidos
"Knockdown of USP8 inhibits prostate cancer cell growth , proliferation , and metastasis and promotes docetaxel 's activity by suppressing the NF-kB signaling pathway Ubiquitin-specific protease 8 ( USP8 ) has been recently reported to be involved in tumorigenesis ."

reach
"These results imply that USP8 plays a vital role in the development and proliferation of PCa cells, indicating that targeting USP8 for PCa treatment is a good idea.The knockdown of USP8 enhanced the anti-proliferative impact of docetaxel in the MTT assay in both PCa cell lines."

reach
"In contrast, USP8 knockdown was found to enhance docetaxel antitumor activity."

reach
"However, the role of USP8 in PCa and whether USP8 has any effects on docetaxel treatment to regulate its effects targeting to enhance docetaxel activity, which may help to suppress the docetaxel resistance in CRPC, are also unclear."

reach
"Besides, we also showed that knocking down of USP8 in PCa cells enhanced the anticancer activity of docetaxel whereas the overexpression of USP8 suppressed the docetaxel activity."

reach
"Notably, the combination treatment of docetaxel and SiUSP8 was found to have the lowest cell survival 65.1 ± 2.4% and 60.4 ± 2.1% in DU145 ( Figure 1C1 ) and PC3 ( Figure 1C2 ) cells, respectively, which were significant compared to control and individual treatments of SiUSP8 and docetaxel.On the other hand, compared to the control group, the USP8 overexpression eliminated the impact of docetaxel in PCa cells."
| 2

reach
"Furthermore, knocking down USP8 enhanced docetaxel’s anticancer activity."

reach
"The USP8 silencing in both PCa cell lines found a significantly decreased IKKα and thereby decreased phosphorylated IκBα and increased IκBα compared to control and docetaxel treatment ( Figures 4A, B )."
| 1 14
| 1 12

reach
"USP8 promotes CSCC progression by enhancing tumor invasion capacity."

eidos
"Our findings indicated that the proliferation , invasion , and stemness of LN229 and T98G cells were markedly suppressed by USP8 inhibition ."

reach
"In conclusion, we demonstrated that USP8 in cancer tissue is an independent prognostic biomarker of CSCC, and high USP8 in CSCC can enhance cell invasion."

reach
"Meanwhile, USP8 deficiency could reduce tumor invasion and migration and tumor size in an immunity-dependent manner, and improve anti-tumor immunogenicity."

reach
"USP8 promotes TGF-β/SMAD-induced epithelial-mesenchymal transition (EMT), invasion, and metastasis in tumor cells."

reach
"Our findings indicated that the proliferation, invasion, and stemness of LN229 and T98G cells were markedly suppressed by USP8 inhibition."

reach
"Moreover, we conducted cellular studies and found that USP8 can significantly upregulate the migration and invasion processes of CSCC cell lines."

reach
"However, both the migration and invasion capacities of CSCC cells were upregulated by USP8 overexpression (XREF_FIG)."

reach
"Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis."

reach
"Knockdown of USP8 Inhibits the Migration and Invasion of Lung Cancer Cells."
| 2

reach
"Down-regulation of USP8 Inhibits Cholangiocarcinoma Cell Proliferation and Invasion."

reach
"Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis."
USP8 affects HIF1A
1 | 7 7
USP8 binds HIF1A.
| 6 7
| 6 5

reach
"The interaction between USP8 and HIF-1alpha has been previously reported by Troilo et al.."

reach
"In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1alpha and consequently the hypoxic adaptive response of neurons may account for this detrimental effect."

reach
"Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin specific protease 8 (USP8) in OGD treated neurons, which led to a suppressed interaction between USP8 and HIF-1alpha and subsequently a reduction in HIF-1alpha protein accumulation in neurons under OGD conditions."

sparser
"In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect."

sparser
"Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8) in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions."

sparser
"The interaction between USP8 and HIF-1α has been previously reported by Troilo et al. ( xref )."

reach
"Second, USP8 directly interacts with HIF-1alpha, and this interaction is increased when Nrdp1 is knocked down."

sparser
"Second, USP8 directly interacts with HIF-1α, and this interaction is increased when Nrdp1 is knocked down."

reach
"To demonstrate a direct interaction between USP8 and HIF-1alpha in OGD treated PC12 cells, we performed co-immunoprecipitation assays and found that HIF-1alpha was precipitated by antibody against USP8, but not by control rabbit IgG."

sparser
"The major findings include: (1) Nrdp1 is significantly upregulated in the ischemic brain tissue and in OGD-treated neuronal cells; (2) overexpression or knockdown of Nrdp1 enhances or attenuates OGD-induced apoptosis in neurons, respectively, and these changes are accompanied by the downregulation or upregulation of Nrdp1’s substrate USP8; and (3) USP8 may directly interact with HIF-1α to prevent its degradation, and under OGD conditions, Nrdp1 may interfere with HIF-1α stabilization via promoting USP8 degradation."
USP8 binds EPAS1 and HIF1A. 2 / 2
| 2

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [75]."

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [ xref ]."
USP8 deubiquitinates HIF1A.
1 | 1
USP8 deubiquitinates HIF1A. 2 / 2
1 | 1

reach
"HIF1alpha deubiquitination by USP8 is essential for ciliogenesis in normoxia."
USP8 affects HGS
| 11 4
USP8 binds HGS.
| 6 4
| 6 1

sparser
"In an immunoprecipitation assay, we did not observe a strong physical interaction between Hrs and USP8 (not shown)."

reach
"USP8 also interacts with the HRS and STAM complex."

reach
"In somatic cells, USP8 interacts with the ESCRT-0 machinery [i.e., STAM (signal transducing adaptor molecule) and HGS (hepatocyte growth factor regulated tyrosine kinase substrate)] and its deubiquitinating activity regulates the endosomal sorting of ubiquitinated cargo between the recycling pathway and the lysosomal degradation pathway [XREF_BIBR]."

reach
"Studies have shown that USP8 also interacts with and deubiquitinate Hrs, demonstrating multiple roles of USP8 in both cargo de-ubiquitination and ESCRT-0 stability during development, which is helpful to address the mechanisms of Hh signaling."

reach
"Although the interaction between Mop, Cbl, Ubpy, and Hrs seems to play a role in the recycling of Fz, our present findings do not exclude a role for other unidentified proteins in this molecular cascade."

reach
"We provide evidence that Ubpy interacts with and deubiquitylates Hrs."

reach
"In an immunoprecipitation assay, we did not observe a strong physical interaction between Hrs and USP8 (not shown)."
SMO binds USP8 and HGS. 2 / 2
| 2

sparser
"However, we found that Hrs blocks Smo phosphorylation ( xref ), whereas USP8 does not xref , suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"It is possible that Hrs competes with USP8 for binding Smo, as Hrs and USP8 directly interact with the same domain of Smo."
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
USP8 deubiquitinates HGS.
| 4
USP8 deubiquitinates HGS. 4 / 4
| 4

reach
"We provide evidence that Ubpy interacts with and deubiquitylates Hrs."

reach
"Mop recruits Ubpy to promote the deubiquitination of Hrs."

reach
"Studies have shown that USP8 also interacts with and deubiquitinate Hrs, demonstrating multiple roles of USP8 in both cargo de-ubiquitination and ESCRT-0 stability during development, which is helpful to address the mechanisms of Hh signaling."

reach
"Previous studies showed that Hrs is deubiquitinated by Ubpy."
USP8 ubiquitinates HGS.
| 1
USP8 leads to the ubiquitination of HGS. 1 / 1
| 1

reach
"Depletion of USP8 by siRNA enhances HRS ubiquitination and inhibits CXCR4 degradation."
HIF1A affects USP8
| 6 7
| 6 5

reach
"The interaction between USP8 and HIF-1alpha has been previously reported by Troilo et al.."

reach
"In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1alpha and consequently the hypoxic adaptive response of neurons may account for this detrimental effect."

reach
"Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin specific protease 8 (USP8) in OGD treated neurons, which led to a suppressed interaction between USP8 and HIF-1alpha and subsequently a reduction in HIF-1alpha protein accumulation in neurons under OGD conditions."

sparser
"In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect."

sparser
"Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8) in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions."

sparser
"The interaction between USP8 and HIF-1α has been previously reported by Troilo et al. ( xref )."

reach
"Second, USP8 directly interacts with HIF-1alpha, and this interaction is increased when Nrdp1 is knocked down."

sparser
"Second, USP8 directly interacts with HIF-1α, and this interaction is increased when Nrdp1 is knocked down."

reach
"To demonstrate a direct interaction between USP8 and HIF-1alpha in OGD treated PC12 cells, we performed co-immunoprecipitation assays and found that HIF-1alpha was precipitated by antibody against USP8, but not by control rabbit IgG."

sparser
"The major findings include: (1) Nrdp1 is significantly upregulated in the ischemic brain tissue and in OGD-treated neuronal cells; (2) overexpression or knockdown of Nrdp1 enhances or attenuates OGD-induced apoptosis in neurons, respectively, and these changes are accompanied by the downregulation or upregulation of Nrdp1’s substrate USP8; and (3) USP8 may directly interact with HIF-1α to prevent its degradation, and under OGD conditions, Nrdp1 may interfere with HIF-1α stabilization via promoting USP8 degradation."
USP8 binds EPAS1 and HIF1A. 2 / 2
| 2

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [75]."

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [ xref ]."
EGF affects USP8
| 8 5
EGF phosphorylates USP8.
| 3 5
EGF phosphorylates USP8. 5 / 5
| 5

sparser
"2 and 3 suggest that the mechanism responsible for EGF-induced Usp8 tyrosine phosphorylation might be the same for EGFR and ErbB2."

sparser
"In EGFR-ErbB2 expressing cells, EGF-induced Usp8 tyrosine phosphorylation was even lower in the presence of PD153035 than the Usp8 tyrosine phosphorylation level observed in unstimulated and mock-trea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As we have demonstrated before, deletion of the MIT-domain in Usp8 results in decreased EGF-induced Usp8 tyrosine phosphorylation [17] ."

sparser
"Collectively, these data demonstrate that the Cbl binding site of the wild-type EGFR and the EGFR-ErbB2 chimera is not required for efficient EGF-induced Usp8 tyrosine phosphorylation or coprecipitati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In cells expressing either EGFR ( Fig. 6 A and C ) or EGFR-ErbB2 ( Fig. 6 B and D), removal of the MIT domain (Usp8 Δ140) resulted in a decrease of the EGF-induced Usp8 tyrosine phosphorylation, when [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
EGF leads to the phosphorylation of USP8 on tyrosine. 3 / 3
| 3

reach
"Moreover, EGF stimulation of EGFR induces USP8 tyrosine phosphorylation while, in contrast, TGF-alpha reduces tyrosine phosphorylation [131]."

reach
"These results show that EGF stimulation of EGFR-ERBB4 CYT-1 triggers USP8 tyrosine phosphorylation and demonstrate that USP8 is part of the ERBB4 signaling cascade."

reach
"This model is supported by our current findings that TGFalpha stimulation of EGFR and EGF stimulation of ERBB2 [52], conditions that are associated with enhanced endosomal recycling and decreased MVB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
EGF activates USP8.
| 3
EGF activates USP8. 3 / 3
| 3

reach
"Collectively, these data demonstrate that the Cbl binding site of the wild-type EGFR and the EGFR-ErbB2 chimera is not required for efficient EGF induced Usp8 tyrosine phosphorylation or coprecipitati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"EGF treatment induced a faster degradation of EGFR protein in HeLa cells expressing WT USP8 compared to mutants, although EGFR protein levels were comparable in these cells under serum starved conditions (XREF_FIG)."

reach
"As we have demonstrated before, deletion of the MIT-domain in Usp8 results in decreased EGF induced Usp8 tyrosine phosphorylation [17]."
EGF inhibits USP8.
| 2
EGF inhibits USP8. 2 / 2
| 2

reach
"In EGFR-ErbB2 expressing cells, EGF induced Usp8 tyrosine phosphorylation was even lower in the presence of PD153035 than the Usp8 tyrosine phosphorylation level observed in unstimulated and mock trea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In cells expressing either EGFR or EGFR-ErbB2, removal of the MIT domain (Usp8 Delta140) resulted in a decrease of the EGF induced Usp8 tyrosine phosphorylation, when compared to Usp8 wt."
CHMP1B affects USP8
4 | 3 6
CHMP1B binds USP8.
4 | 1 6
4 | 1 6

sparser
"Eleven confirmed hits inhibited the USP8::CHMP1B interaction within a range of 30% to 70% inhibition at 50 µM, while they were inactive on a set of other PPI interfaces demonstrating the feasibility of specifically disrupting this particular interface."

No evidence text available

sparser
"As anticipated from earlier studies, a deletion of the MIM (Microtubule Interacting and Trafficking domain Interacting Motif) domain or mutation of two conserved leucine residues, L192 and L195, in this domain respectively abolished or strongly impeded the USP8::CHMP1B interaction."

sparser
"The USP8 MIT domain binds tightly to CHMP1B and more weakly to a subset of other CHMPs ( xref )."

sparser
"Interaction of CHMP1B with USP8 occurs via α-helices 4, 5, and 6 of CHMP1B."

No evidence text available

No evidence text available

No evidence text available

reach
"Full-length CHMP1B and alpha-helices 4, 5 and 6 interacted with Flag-USP8 in this assay (XREF_FIG)."

sparser
"The function of USP8 at the endocytic pathway level partly relies on binding to and deubiquitination of the Endosomal Sorting Complex Required for Transport (ESCRT) protein CHMP1B. In the aim of finding chemical inhibitors of the USP8::CHMP1B interaction, we performed a high-throughput screening campaign using an HTRF® assay to monitor the interaction directly in lysates of cells co-expressing both partners."
CHMP1B activates USP8.
| 2
CHMP1B activates USP8. 2 / 2
| 2

reach
"Furthermore, the finding that CHMP1B is a target of USP8 may shed new light in the future on understanding its contribution to membrane receptor trafficking, resistance to chemotherapy or EGFR stabilization in Cushing 's disease."

reach
"CHMP1B is a target of USP8 and UBPY regulated by ubiquitin during endocytosis."
USP8 affects cell growth
| 9
| 9

reach
"USP8 was originally identified to enhance cell growth as its expression increases upon serum stimulation in cancer cells."

reach
"USP8 silencing significantly inhibits PCa cell growth, survival, and migration and promotes apoptosis by increasing cleaved Caspase 3 and cleaved Caspase 9."

reach
"XREF_BIBR Ubiquitin specific peptidases (USP8) was originally identified to enhance cell growth as its expression increases upon serum stimulation in cancer cells."

reach
"Knockdown of USP8 inhibits prostate cancer cell growth, proliferation, and metastasis and promotes docetaxel's activity by suppressing the NF-kB signaling pathway."

reach
"In contrast, USP8 knockdown suppressed melanoma cell growth, survival and migration, and augmented the inhibitory effects of therapeutic drugs."

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."

reach
"This study also shows that USP8 overexpression promotes PCa cell growth, survival, and migration and suppresses apoptosis."

reach
"USP8 is known to enhance cell growth as its expression increases in cancer cell XREF_BIBR."

reach
"Small molecule inhibitors of USP8 (HBX90,397 and HBX 90,659) have been shown to inhibit HCT116 and PC3 cell growth, and to display specificity for USP8 among a panel of cysteine proteases [XREF_BIBR]."
USP8 affects Ubiquitin
| 8 3
USP8 binds Ubiquitin.
| 1 3
| 1 1

sparser
"Interestingly, the crystal structure of USP8-Ubv complex shows a significantly different mode of binding than USP8-UB, suggesting phage selection using the Ubv library could find alternative binding modes with DUBs that maximize binding affinity. xref and xref also generated Ubvs for binding to DUBs of various families as well as viral DUBs."

reach
"Although there is no structure available of a USP8 and ubiquitin complex, the closely related USP domain of USP2 has been solved in the presence of ubiquitin XREF_BIBR."

sparser
"We demonstrate that the pivotal β-cell mitophagy regulator, CLEC16A, is an E3 ligase that forms a ubiquitin-dependent tripartite complex with RNF41/NRDP1 and USP8."
| 1

sparser
"There was evidence that Magel2 was involved in the leptin-POMC of the hypothalamus to maintain the energy balance of the body.[ xref ]Wijesuriya et al have found that MAGEL2 and Necdin connected leptin receptor (LepR) to the USP8-RNF41 ubiquitin complex through the LepR adapter protein, IRS4."
USP8 activates Ubiquitin.
| 4
| 4

reach
"And USP8 catalyzes ubiquitin removal from both Lys48 linkage and Lys63 linkage polyubiquitination chains."

reach
"Moreover, P5091 inhibits USP7-, but not USP2- or USP8 mediated cleavage of poly K48 linked ubiquitin chains (visualized by the presence or absence of mono-ubiquitin) (XREF_SUPPLEMENTARY)."

reach
"USP8 enhances mitophagy by removing lysine-6-linked ubiquitin from parkin, promoting its turnover [XREF_BIBR]."

reach
"71 In contrast to PAR2, USP8 (or AMSH) does not impact CXCR4 ubiquitination but instead modulates the ubiquitin status of ESCRT-0 that is ubiquitinated by the E3 ligase AIP4, 23 reinforcing the idea that ubiquitination of the transport machinery represents an important regulatory event in GPCR trafficking."
USP8 inhibits Ubiquitin.
| 3
| 3

reach
"In Drosophila melanogaster, UBPY silencing enhanced neurodegenerative TDP-43 phenotypes and the accumulation of insoluble high molecular weight TDP-43 and ubiquitin species."

reach
"This zinc-finger ribbon seems to be in the contracted " closed-hand " configuration seen in USP8 that blocks ubiquitin access (XREF_FIG)."

reach
"This zinc-finger ribbon (observed also in USP2, USP8 and USP21 structures) is in the contracted ' closed-hand ' configuration seen in USP8, which was proposed to block ubiquitin access XREF_BIBR."
USP8 affects MCPH1
3 1 | 2 6
USP8 binds MCPH1.
3 | 1 6
USP8 binds BIRC6 and MCPH1. 5 / 5
| 5

sparser
"Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex."

sparser
"Specifically, the BIR is dispensible for the scaffold function of BRUCE in tethering USP8 and BRIT1 forming the nuclear BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"The formation of the BRUCE-USP8-BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

sparser
"In the recently elucidated role of BRUCE in the regulation of DNA damage signaling and repair, neither the BIR or UBC is required for the scaffold function of BRUCE in the formation of BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"Together, these results indicate that subsequent to the formation of the BRUCE-USP8-BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
3 | 1 1

No evidence text available

sparser
"USP8 forms a complex with the early DDR factor BRIT1."

reach
"USP8 forms a complex with the early DDR factor BRIT1."

No evidence text available

No evidence text available
USP8 deubiquitinates MCPH1.
1 | 1
USP8 deubiquitinates MCPH1. 2 / 2
1 | 1

"BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1"

reach
"Upon DSB induction, BRUCE promoted USP8-mediated deubiquitination of BRIT1 triggering its release and subsequent binding to γ-H2AX which is located in DSB-flanking chromatin where it facilitates chromatin relaxation."
USP8 affects KDR
| 8 1
USP8 activates KDR.
| 3
USP8 activates KDR. 3 / 4
| 3

reach
"Perturbed VEGFR2 endosomal trafficking caused by USP8 depletion could modulate endosome linked signal transduction."

reach
"VEGFR2 accumulation also occurred when cells were treated with individual USP8 siRNAs to limit off-target effects."

reach
"VEGFR2 also accumulated in EEA1 positive early endosomes when cells were treated with individual USP8 siRNAs to limit off-target effects."
USP8 ubiquitinates KDR.
| 1 1
USP8 leads to the ubiquitination of KDR. 2 / 3
| 1 1

reach
"USP8 depletion increased levels of this K48- and K63 linked polyubiquitinated species of VEGFR2."

sparser
"We now provide evidence that USP8 de‐ubiquitinates VEGFR2."
USP8 deubiquitinates KDR.
| 3
USP8 deubiquitinates KDR. 3 / 3
| 3

reach
"We now provide evidence that USP8 de-ubiquitinates VEGFR2."

reach
"Conversely, the de-ubiquitinating enzyme, USP8, is shown to mediate de-ubiquitination of VEGFR2, regulating VEGFR2 trafficking, proteolysis, and signal transduction 39."

reach
"USP8 depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system."
USP8 inhibits KDR.
| 1
USP8 inhibits KDR. 1 / 2
| 1

reach
"VEGF-A-stimulated VEGFR2 signal transduction is perturbed by USP8 depletion."
USP8 affects BRIT1
| 12
USP8 deubiquitinates BRIT1.
| 6
USP8 deubiquitinates BRIT1. 6 / 6
| 6

reach
"Together these results demonstrated that the UBC but not the BIR domain is required for BRUCE to promote USP8 deubiquitination of BRIT1 in response to IR exposure."

reach
"Deubiquitination of BRIT1 by BRUCE dependent USP8 is an intermediate step between the complex formation and BRIT1 recruitment to DSB."

reach
"BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1."

reach
"BRIT1 is deubiquitylated and stabilized by USP8 with the help of the scaffold protein BRUCE, tightly regulating the action of BRIT1 at damaged sites."

reach
"Following DSB induction, BRUCE promotes USP8 mediated deubiquitination of BRIT1, a prerequisite for BRIT1 to be released from the complex and recruited to DSB by binding to gamma-H2AX."

reach
"Following exposure to IR, USP8 promotes BRIT1 deubiquitination in BRUCE dependent manner, leading to dissociation of BRIT1 from the platform and consequent recruitment of it to the DSB sites by binding to gamma-H2AX."
USP8 binds BRIT1.
| 6
USP8 binds BIRC6 and BRIT1. 6 / 6
| 6

reach
"Given the fact that the integrity of the BRUCE, USP8, and BRIT1 complex is essential for targeting BRIT1 to DSB, whether the observed UBC requirement is attributable to its contribution to maintaining the complex integrity was examined."

reach
"Mutation or deletion of the BRUCE UBC domain did not disrupt the BRUCE, USP8, and BRIT1 complex, but impaired deubiquitination and consequent recruitment of BRIT1 to DSB."

reach
"Once deubiquitinated, BRIT1 is released from the BRUCE, USP8, and BRIT1 complex and targeted to DSBs by binding to gamma-H2AX at sites of DSB [XREF_BIBR], where BRIT1 recruits the SWI/SNF chromatin remodeling complex to facilitate relaxation of chromatin configuration for the access of repair factors to damaged chromatin [XREF_BIBR]."

reach
"The formation of the BRUCE, USP8, and BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

reach
"This deubiquitination triggers the release of BRIT1 from the BRUCE, USP8, and BRIT1 complex and consequently released BRIT acquires the ability to be recruited to sites of DNA damage by binding to phosphorylated H2AX (gamma-H2AX)."

reach
"Together, these results indicate that subsequent to the formation of the BRUCE, USP8, and BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
PRKN affects USP8
| 4 7
| 4 7

reach
"The results showed that NaHS treatment increased the USP8/parkin interaction in db/db cardiac tissues (Fig. 5C)."

sparser
"Our results showed that the effects of exogenous H 2 S on USP8 deubiquitylation and the interaction of USP8 with parkin were blocked with DTT treatment ( xref )."

sparser
"Dithiothreitol, a reducing agent that reverses sulfhydration-mediated covalent modification, increased the ubiquitylation level of parkin, abolished the effects of exogenous H 2 S on USP8 deubiquitylation and suppressed the interaction of USP8 with parkin in neonatal rat cardiomyocytes treated with high glucose, oleate and palmitate."

sparser
"Our results showed that exogenous H 2 S could result in the S-sulfhydration of USP8 under hyperglycemia and hyperlipidemia, leading to the enhanced interaction of USP8 with parkin and the translocation of parkin into mitochondria."

reach
"Our results showed that hyperglycemia and hyperlipidemia decreased the translocation of parkin in the mitochondrial outer membrane and decreased the interaction between USP8 and parkin."

sparser
"Our results showed that hyperglycemia and hyperlipidemia decreased the translocation of parkin in the mitochondrial outer membrane and decreased the interaction between USP8 and parkin."

sparser
"Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in the pathway."

reach
"Our results showed that the S-sulfhydration level of USP8 was obviously decreased in vivo and in vitro under hyperglycemia and hyperlipidemia, however, exogenous H 2 S could reverse this effect and promote USP8/parkin interaction."

sparser
"Further, DTT inhibited the interaction of USP8 with parkin."

sparser
"In the diabetic heart, ubiquitin specific peptidase 8 (USP8) has been implicated: H 2 S was found to increase the association of parkin with USP8."
LRIG1 affects USP8
1 | 6 5
LRIG1 binds USP8.
1 | 5 5
1 | 5 5

reach
"Collectively, these results suggest that SAIT301 triggers degradation of LRIG1 by interfering the interaction of USP8 and LRIG1, and USP8 regulates ubiquitin modification and stability of LRIG1."

reach
"Interestingly, SAIT301 treatment markedly decreased the interaction of LRIG1 and USP8 (XREF_FIG)."

sparser
"Interestingly, SAIT301 triggers LRIG1/Met degradation by interfering with LRIG1-USP8 interaction."

reach
"SAIT301 triggers degradation of LRIG1 by inhibiting the interaction of LRIG1 and USP8, which regulates ubiquitin modification and stability of LRIG1."

sparser
"We also identified USP8 as a LRIG1-specific deubiquitinating enzyme, reporting the interaction between USP8 and LRIG1 for the first time."

sparser
"Collectively, these results suggest that SAIT301 triggers degradation of LRIG1 by interfering the interaction of USP8 and LRIG1, and USP8 regulates ubiquitin modification and stability of LRIG1."

sparser
"We demonstrated that SAIT301 inhibits the interaction of LRIG1 and USP8."

reach
"We also identified USP8 as a LRIG1 specific deubiquitinating enzyme, reporting the interaction between USP8 and LRIG1 for the first time."

sparser
"Interestingly, SAIT301 treatment markedly decreased the interaction of LRIG1 and USP8 ( xref )."

No evidence text available
LRIG1 activates USP8.
| 1
LRIG1 activates USP8. 1 / 1
| 1

reach
"In summary, the findings in the current study highlight LRIG1 mediated Met degradation and the implication of USP8 in the regulation of LRIG1 ubiquitination by a Met targeting antibody."
USP8 affects ERBB2
1 | 5 3
USP8 binds ERBB2.
| 3
| 3

sparser
"Our current findings further demonstrate that Usp8 binds to ErbB2 and that Usp8 tyrosine phosphorylation is dependent on ErbB2- ( Fig. 4 ) and Src- kinase ( Fig. 5 ) activities, thereby extending our [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Given the impaired downregulation of ErbB2, we have investigated in the present study whether ErbB2 and Usp8 functionally interact."

sparser
"Moreover, we show that Usp8 interacts with ErbB2 and is tyrosine phosphorylated in a ErbB2- and Src kinase-dependent manner, although its tyrosine phosphorylation is to a lesser extent than in the cas[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 deubiquitinates ERBB2.
1 | 2
USP8 deubiquitinates ERBB2. 3 / 3
1 | 2

reach
"We recently showed that Usp8 also deubiquitinates ERBB2, albeit to a much lesser extent than EGFR [17]."

"ERBB2 is a target for USP8-mediated deubiquitination"

reach
"We recently showed that Usp8 also deubiquitinates ErbB2, albeit to a much lesser extent than EGFR [10]."
USP8 inhibits ERBB2.
| 2
USP8 inhibits ERBB2. 2 / 2
| 2

reach
"The USP8 inhibited HER-2 positive GC cell proliferation and migration in vivo and in vitro and probably served as a novel potential therapeutic biomarker for HER-2 positive GC."

reach
"USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K and AKT Signaling Pathway."
USP8 phosphorylates ERBB2.
| 1
USP8 leads to the phosphorylation of ERBB2 on methionine. 1 / 1
| 1

reach
"Western blotting confirmed that knockdown of USP8 not only reduced RTK phosphorylation, but also the total levels of EGFR, ERBB2, ERBB3, and MET in H1975 and H1650 cells (XREF_FIG)."
USP8 affects CFLAR
4 1 | 4 2
USP8 binds CFLAR.
4 | 2
4 | 1

sparser
"However, Jeong et al. [ xref ] showed that USP8 directly interacts with the caspase-like domain in c-FLIP L to induce deubiquitination and stabilization of cFLIP L , but not cFLIP S . Depletion of USP8 destabilized cFLIP L resulting in sensitization to DR-induced apoptosis."

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP8 binds ITCH and CFLAR. 1 / 1
| 1

sparser
"USP8-regulated ITCH binding to c-FLIP mediates c-FLIP ubiquitination in cancer cells incubated with 9F7-F11."
USP8 deubiquitinates CFLAR.
1 | 2
USP8 deubiquitinates CFLAR. 3 / 3
1 | 2

"USP8 directly deubiquitylates and stabilizes FLIPL"

reach
"USP8 and USP9X deubiquitinate ITCH to induce ubiquitination and degradation of the anti-apoptotic protein c-FLIP, leading to apoptosis in glioblastoma [XREF_BIBR], or to anoikis in pancreatic ductal adenocarcinoma [XREF_BIBR]."

reach
"However, Jeong et al. [98] showed that USP8 directly interacts with the caspase-like domain in c-FLIP to induce deubiquitination and stabilization of cFLIP , but not cFLIP ."
USP8 ubiquitinates CFLAR.
| 2
Modified USP8 leads to the ubiquitination of CFLAR. 2 / 2
| 2

reach
"Overexpression of USP8 increased c-FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance (XREF_FIG)."

reach
"Overexpression of USP8 increased c-FLIP S ubiquitination, decreased c-FLIP S half-life, decreased c-FLIP S steady-state levels, and decreased TRAIL resistance."
HGS affects USP8
| 7 4
HGS binds USP8.
| 6 4
| 6 1

sparser
"In an immunoprecipitation assay, we did not observe a strong physical interaction between Hrs and USP8 (not shown)."

reach
"USP8 also interacts with the HRS and STAM complex."

reach
"In somatic cells, USP8 interacts with the ESCRT-0 machinery [i.e., STAM (signal transducing adaptor molecule) and HGS (hepatocyte growth factor regulated tyrosine kinase substrate)] and its deubiquitinating activity regulates the endosomal sorting of ubiquitinated cargo between the recycling pathway and the lysosomal degradation pathway [XREF_BIBR]."

reach
"Studies have shown that USP8 also interacts with and deubiquitinate Hrs, demonstrating multiple roles of USP8 in both cargo de-ubiquitination and ESCRT-0 stability during development, which is helpful to address the mechanisms of Hh signaling."

reach
"Although the interaction between Mop, Cbl, Ubpy, and Hrs seems to play a role in the recycling of Fz, our present findings do not exclude a role for other unidentified proteins in this molecular cascade."

reach
"We provide evidence that Ubpy interacts with and deubiquitylates Hrs."

reach
"In an immunoprecipitation assay, we did not observe a strong physical interaction between Hrs and USP8 (not shown)."
SMO binds USP8 and HGS. 2 / 2
| 2

sparser
"However, we found that Hrs blocks Smo phosphorylation ( xref ), whereas USP8 does not xref , suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"It is possible that Hrs competes with USP8 for binding Smo, as Hrs and USP8 directly interact with the same domain of Smo."
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
HGS activates USP8.
| 1
HGS activates USP8. 1 / 1
| 1

reach
"Overexpression of Hrs or a dominant negative mutant of SKD1, proteins that play roles in the endosomal sorting of ubiquitinated receptors, caused the accumulation of endogenous UBPY on exaggerated endosomes."
EPG5 affects USP8
| 3 8
| 3 8

reach
"The results showed that USP8 is immunoprecipitated by EPG5, indicating that there is an interaction between EPG5 and USP8 (Fig. 3b)."

sparser
"Co-IP assay confirmed the interaction between EPG5 and USP8 in ESCs (Fig.  xref )."

sparser
"Furthermore, immunofluorescence microscopy showed that EPG5 did directly interact with USP8 in ESCs (Fig.  xref )."

sparser
"The results showed that USP8 is immunoprecipitated by EPG5, indicating that there is an interaction between EPG5 and USP8 (Fig.  xref )."

sparser
"These data support that EPG5 binds to USP8."

reach
"These data support that EPG5 binds to USP8."

reach
"To examine whether USP8 binds to EPG5 in cells, we transfected Flag-tagged Epg5 and/or HA-tagged Usp8 in HEK293T cells and performed coimmunoprecipitation (co-IP) assays."

sparser
"To examine whether USP8 binds to EPG5 in cells, we transfected Flag-tagged Epg5 and/or HA-tagged Usp8 in HEK293T cells and performed coimmunoprecipitation (co-IP) assays."

sparser
"EPG5 directly interacts with USP8."

sparser
"To further confirm that EPG5 interacts with USP8 in ESCs, stable ESC lines harboring HA- Epg5 or Myc- Usp8 vectors were established."
USP8 affects POMC
| 10
USP8 activates POMC. 8 / 8
| 8

reach
"For the first time, we showed that USP8 knockdown or gefitinib treatment significantly reduced ACTH secretion in primary USP8 mutated corticotrophin adenoma cells, but not in wild-type cells."

reach
"USP8 knockdown leads to reduce EGFR protein and inhibits ACTH secretion."

reach
"USP8 mutated tumors are more common in females, and are associated with earlier onset, a smaller size, and increased ACTH production."

reach
"We further showed that USP8 knockdown or gefitinib (a clinically available EGFR inhibitor) treatment significantly reduced ACTH secretion in primary USP8 mutated corticotrophin adenoma cells, but not in wild-type cells."

reach
"Because EGFR signaling increases POMC transcription and secretion of ACTH [XREF_BIBR], increased USP8 activity causes elevated ACTH production."

reach
"The presence of such associations is supported by the finding that USP8 knockdown or EGFR inhibition attenuates ACTH secretion in primary USP8 mutated tumor cells [XREF_BIBR]."

reach
"We will provide an overview of corticotroph tumorigenesis in the context of hypothalamic-pituitary-adrenal (HPA) axis regulation with an emphasis on the role of the glucocorticoid receptor in the resistance to the negative feedback of cortisol that occurs in CD, and we will explore the role of epidermal growth factor receptor (EGFR) signaling in ACTH hyper-secretion and corticotroph cell proliferation and the recent discovery of somatic ubiquitin specific peptidase 8 (USP8) mutations in a significant number of patients with sporadic CD with an emphasis on therapeutic implications."

reach
"USP8 knockdown using shRNA in primary corticotroph adenoma cells effectively reduced ACTH production."
Mutated USP8 activates POMC. 2 / 2
| 2

reach
"It is expected that USP8 mutations deregulate these molecules to drive ACTH production and secretion."

reach
"While USP8 mutations were less likely to enhance tumorous ACTH hypersecretion via EGFR mediated activation, the presence of USP8 mutations may predict favorable responses to the somatostatin analog pasireotide, which exhibits high affinity for SSTR5."
| 4 6
| 4 4

eidos
"Usp8 promotes tumor cell migration through activating the JNK pathway ."

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."

eidos
"Knockdown of USP8 inhibits prostate cancer cell growth , proliferation , and metastasis and promotes docetaxel 's activity by suppressing the NF-kB signaling pathway Ubiquitin-specific protease 8 ( USP8 ) has been recently reported to be involved in tumorigenesis ."

eidos
"USP8 regulates NF-kappaB activation through EGFR and PI3K stabilization to promote PCa cell proliferation and survival In multiple studies ( 29-32 ) , the EGFR is a substrate of USP8 deubiquitination , while USP8 has been shown to enhance gastric cancer cell proliferation and metastasis via the PI3K / AKT signaling pathway ( 30 ) ."

reach
"Knockdown of USP8 inhibits prostate cancer cell growth, proliferation, and metastasis and promotes docetaxel's activity by suppressing the NF-kB signaling pathway."

reach
"USP8 promotes TGF-β/SMAD-induced epithelial-mesenchymal transition (EMT), invasion, and metastasis in tumor cells."

reach
"In multiple studies (29–32), the EGFR is a substrate of USP8 deubiquitination, while USP8 has been shown to enhance gastric cancer cell proliferation and metastasis via the PI3K/AKT signaling pathway (30)."

eidos
"Here , we find that the ubiquitin-specific protease 8 ( Usp8 ) promotes tumor cell migration through activating the c-Jun N-terminal kinase ( JNK ) pathway ."
| 2

reach
"XREF_BIBR, XREF_BIBR Therefore, it can be inferred that down-regulation of USP8 may inhibit the proliferation and even metastasis of GC through this pathway."

reach
"USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K and AKT Signaling Pathway."
USP8 affects GRAP2
5 2 | 1 1
5 2 | 1

reach
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP8 binds BLNK, GAB2, and GRAP2. 1 / 1
| 1

sparser
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."
USP8 affects FLVCR1
| 10
USP8 activates FLVCR1.
| 9
USP8 activates FLVCR1. 9 / 9
| 9

reach
"USP8 silencing significantly inhibits PCa cell growth, survival, and migration and promotes apoptosis by increasing cleaved Caspase 3 and cleaved Caspase 9."

reach
"Therefore, similar to the wound healing assay, it could be stated that USP8 overexpression increased the PCa cell migration and diminished the effect of docetaxel on PCa migration."

reach
"Consequently, significantly increased EGFR and PI3K were also found in USP8-overexpressed PCa cell lines compared to the control."

reach
"The data from Western blotting showed that there was a significantly increased IKKα, phosphorylated IκBα and p65, and p65 found in USP8-overexpressed PCa cells but decreased IκBα compared to control and thereby upregulating the NF-κB activation ( Figures 4C, D )."

reach
"Overexpression of USP8 promotes PCa cell migration and diminished docetaxel activity."

reach
"Silencing of USP8 suppresses PCa cell migration and promotes docetaxel activity."

reach
"This study also shows that USP8 overexpression promotes PCa cell growth, survival, and migration and suppresses apoptosis."

reach
"Its overexpression increased the PCa cell migration and diminished the healing action of docetaxel in both cells.Similar to the wound healing assay, overexpression of USP8 resulted in the highest number of migrated cells for both Du145 and PC3 cells in the Transwell assay, which showed statistical significance compared to all other treatment group cells ( Figure 3B )."

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."
USP8 inhibits FLVCR1.
| 1
USP8 inhibits FLVCR1. 1 / 1
| 1

reach
"In contrast, the elevated expression of USP8 greatly reduced the proportion of apoptotic PCa cells ( Figure 5B ) and reduced the cleaved Caspase 3 and cleaved Caspase 9 which were found in DU145 and PC3 cells by USP8 overexpression ( Figures 6A, B )."
USP8 affects ERBB3
| 9 1
USP8 inhibits ERBB3.
| 3
USP8 inhibits ERBB3. 3 / 3
| 3

reach
"Erratum: Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation [Corrigendum]."

reach
"All these results indicated that down-regulation of USP8 could inhibit the proliferation of HER-3 positive cells, NCI-N87 and MKN-45, in vivo."

reach
"Down-Regulation of USP8 Promotes the Degradation of HER-3."
USP8 increases the amount of ERBB3.
| 2
USP8 increases the amount of ERBB3. 2 / 2
| 2

reach
"Western blotting confirmed that knockdown of USP8 not only reduced RTK phosphorylation, but also the total levels of EGFR, ERBB2, ERBB3, and MET in H1975 and H1650 cells (XREF_FIG)."

reach
"These results are opposite of the results seen by Niendorf et al. [130] showing that deletion of USP8 leads to lower level of ERBB3."
USP8 decreases the amount of ERBB3.
| 2
USP8 decreases the amount of ERBB3. 2 / 2
| 2

reach
"Down-regulation of USP8 inhibited cell proliferation and cell metastasis and also reduced the HER-3 expression."

reach
"USP8 or USP9X silencing increased HER3 protein level in basal conditions (medium alone) in BxPC3 cells, suggesting that each deubiquitinase promotes basal HER3 degradation by stabilizing ITCH, as proposed for USP8 [XREF_BIBR]."
USP8 activates ERBB3.
| 2
USP8 activates ERBB3. 2 / 2
| 2

reach
"Moreover, down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle."

reach
"These results indicated that down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle."
USP8 binds ERBB3.
| 1
| 1

sparser
"In addition, antibody treatment disrupted the basal USP8-HER3 interaction to favor ITCH-mediated HER3 ubiquitination and proteasomal degradation."
MCPH1 affects USP8
3 | 1 6
USP8 binds BIRC6 and MCPH1. 5 / 5
| 5

sparser
"Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex."

sparser
"Specifically, the BIR is dispensible for the scaffold function of BRUCE in tethering USP8 and BRIT1 forming the nuclear BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"The formation of the BRUCE-USP8-BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

sparser
"In the recently elucidated role of BRUCE in the regulation of DNA damage signaling and repair, neither the BIR or UBC is required for the scaffold function of BRUCE in the formation of BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"Together, these results indicate that subsequent to the formation of the BRUCE-USP8-BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
3 | 1 1

No evidence text available

sparser
"USP8 forms a complex with the early DDR factor BRIT1."

reach
"USP8 forms a complex with the early DDR factor BRIT1."

No evidence text available

No evidence text available
GRAP2 affects USP8
5 2 | 1 1
5 2 | 1

reach
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP8 binds BLNK, GAB2, and GRAP2. 1 / 1
| 1

sparser
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."
USP8 affects TARDBP
3 2 | 4
USP8 binds TARDBP.
3 2 |
3 2 |

No evidence text available

"The ubiquitin-conjugating enzyme UBE2E3 and ubiquitin-isopeptidase Y (UBPY) were identified, in a yeast two-hybrid screen, to interact with TDP-43 and this interaction is proposed to enhance the ubiquitination and accumulation of its insoluble high molecular weight aggregates (Hans et al., 2014)."

No evidence text available

No evidence text available

"The ubiquitin-conjugating enzyme UBE2E3 and ubiquitin-isopeptidase Y (UBPY) were identified, in a yeast two-hybrid screen, to interact with TDP-43 and this interaction is proposed to enhance the ubiquitination and accumulation of its insoluble high molecular weight aggregates (Hans et al., 2014)."
USP8 inhibits TARDBP.
| 3
USP8 inhibits TARDBP. 3 / 3
| 3

reach
"Furthermore, knockdown of UBPY promotes formation of insoluble TDP-43 aggregates and induced neurotoxicity in D. melanogaster."

reach
"In contrast with α-synuclein [79], USP8 deficiency enhanced TDP-43 neurotoxicity in Drosophila."

reach
"In Drosophila melanogaster, UBPY silencing enhanced neurodegenerative TDP-43 phenotypes and the accumulation of insoluble high molecular weight TDP-43 and ubiquitin species."
USP8 ubiquitinates TARDBP.
| 1
USP8 leads to the ubiquitination of TARDBP-K263E. 1 / 1
| 1

reach
"Conversely, UBE2E3 silencing and expression of UBPY reduced TDP-43 (K263E) ubiquitination."
USP8 affects RNF128
1 1 | 3 4
USP8 binds RNF128.
1 1 | 4
1 | 2

sparser
"Otub1 forms a trimolecular complex with USP8 and GRAIL, and upregulated Otub1 promotes GRAIL's proteosomal degradation."

sparser
"USP8 can form a complex with RNF128 and OTUB1 to regulate the anergy of T-cells mediated by RNF128 ( xref )."

No evidence text available
1 | 2

sparser
"Grail forms a ternary complex with Otub-1 and USP8, regulating T-cell anergy xref , xref ."

sparser
"The proteasome has both ubiquitin ligases and DUBs that associate with it (Crosas et al., 2006) , and several DUB-ligase pairs interact directly, including BRCC36-BRCA1, BAP1-BRCA1, USP4-Ro52, USP7-MDM2, USP8-GRAIL, USP20-pVHL, USP33-pVHL and USP44-APC (Kee and Huibregtse, 2007; Marfany and Denuc, 2008; Ventii and Wilkinson, 2008) ."

No evidence text available
USP8 deubiquitinates RNF128.
| 2
USP8 deubiquitinates RNF128. 2 / 2
| 2

reach
"These data further demonstrate that the two isoforms of Otubain 1 have opposing effects on GRAIL and that Otubain 1 ARF-1 recruits the ubiquitin specific protease 8 (USP-8) to promote GRAIL deubiquitination and stabilization."

reach
"This unexpected function of otubain-1 might be mediated through the inhibition of USP8, a DUB that binds to and deubiquitylates GRAIL; however, it is not known how otubain-1 might inhibit USP8."
USP8 activates RNF128.
| 1
USP8 activates RNF128. 1 / 1
| 1

reach
"Since Otub1was previously shown to interact with USP8, we asked whether it had any effect on USP8 modulation of GRAIL stability."
RNF128 affects USP8
1 1 | 2 5
RNF128 binds USP8.
1 1 | 4
1 | 2

sparser
"Otub1 forms a trimolecular complex with USP8 and GRAIL, and upregulated Otub1 promotes GRAIL's proteosomal degradation."

sparser
"USP8 can form a complex with RNF128 and OTUB1 to regulate the anergy of T-cells mediated by RNF128 ( xref )."

No evidence text available
1 | 2

sparser
"Grail forms a ternary complex with Otub-1 and USP8, regulating T-cell anergy xref , xref ."

sparser
"The proteasome has both ubiquitin ligases and DUBs that associate with it (Crosas et al., 2006) , and several DUB-ligase pairs interact directly, including BRCC36-BRCA1, BAP1-BRCA1, USP4-Ro52, USP7-MDM2, USP8-GRAIL, USP20-pVHL, USP33-pVHL and USP44-APC (Kee and Huibregtse, 2007; Marfany and Denuc, 2008; Ventii and Wilkinson, 2008) ."

No evidence text available
RNF128 ubiquitinates USP8.
| 1 1
RNF128 ubiquitinates USP8. 2 / 2
| 1 1

reach
"These data suggest a reciprocal E3-DUB relationship in which GRAIL can ubiquitinate USP8, and ubiquitinated USP8 can de-ubiquitinate GRAIL."

sparser
"These data suggest a reciprocal E3-DUB relationship in which GRAIL can ubiquitinate USP8, and ubiquitinated USP8 can de-ubiquitinate GRAIL."
RNF128 increases the amount of USP8.
| 1
RNF128 increases the amount of ubiquitinated USP8. 1 / 1
| 1

reach
"Furthermore, the presence of wild-type GRAIL along with USP8 increased the amount of ubiquitinated USP8, which was further enhanced when the DUB activity of USP8 was abolished."
USP8 affects TMEM79
| 8
| 6

sparser
"It seems conceivable that the Tmem79-Usp8 pair may have a primordial function in Wnt/FZD signaling in pre-bilaterians ( xref ; xref ), and that the pair have experienced losses in protostomes related to the loss of Wnt and Wnt antagonist genes."

sparser
"TMEM79 is associated with USP8 and inhibits its deubiquitination of FZD."

sparser
"Conversely TMEM79-USP8 interaction was unaffected in FZD null cells in which all 10 FZD genes have been deleted ( xref ; xref ), and is thus not mediated by FZDs."

sparser
"Investigations in cnidarians and basal protostomes will help to address the origin of Tmem79-Usp8 specificity in Wnt/FZD signaling."

sparser
"We therefore investigated TMEM79-USP8 biochemical and functional relationships."

sparser
"We further performed a phylogenic analysis of the Usp8 gene given the Tmem79-Usp8 relationship we uncovered."
FZD binds USP8 and TMEM79. 2 / 2
| 2

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"These data together suggest that the assembly of the FZD-USP8-TMEM79 complex, in which USP8 action on FZD is inhibited specifically, probably is multivalent in nature and involves additional proteins yet to be identified."
USP8 affects PI3K
| 1 7
USP8 activates PI3K.
| 1 3
USP8 activates PI3K. 4 / 4
| 1 3

reach
"This current study showed that the EGFR, PI3K, and NF-κB signaling is downregulated and upregulated in PCa by USP8 silencing and overexpressing, respectively ( Figure 4 )."

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."

reach
"In contrast, the USP8-specific siRNA reduced EGFR and PI3K, suppressing the NF-kB signal."

eidos
"Thereby , together with these data , it can be concluded that the elevated level of USP8 not only increases the expression of EGFR , PI3K , and P-Akt but also might increase the PI3K and P-Akt expression over EGFR silencing where the PI3K and P-Akt well established the downstream target of EGFR ( Figures 6C , D ) ."
USP8 inhibits PI3K.
| 2
USP8 inhibits PI3K. 2 / 2
| 2

reach
"In conclusion, USP8 inhibited lipopolysaccharide-triggered inflammation and pyroptosis in human bronchial epithelial cells by activating PI3K/AKT signaling and inhibiting NF-κB signaling pathway."

reach
"These results demonstrated that knockdown of USP8 promoted cell apoptosis of lung cancer cells by regulating the PI3K/AKT pathway."
USP8 increases the amount of PI3K.
| 2
USP8 increases the amount of PI3K. 2 / 2
| 2

reach
"Although the decreased PI3K and P-Akt levels were found by silenced EGFR, the overexpressed USP8 was shown to increase PI3K/P-Akt expression over EGFR silencing and thereby increase the NF-kB signal activation ( Figure 7 )."

reach
"Thereby, together with these data, it can be concluded that the elevated level of USP8 not only increases the expression of EGFR, PI3K, and P-Akt but also might increase the PI3K and P-Akt expression over EGFR silencing where the PI3K and P-Akt well established the downstream target of EGFR ( Figures 6C, D )."
USP8 affects ITCH
1 | 3 4
USP8 binds ITCH.
| 4
| 3

sparser
"For the interaction of Usp8 and Itch, it has been described that the deubiquitinase Usp8 removes ubiquitin chains on the E3-ligase Itch, which increases its activity towards cFLIP S [ xref ]."

sparser
"One such example has been described for the Itch-Usp8 ‘partnership’, where Usp8 increases the activity of Itch by deubiquitination [ xref ]."

sparser
"Altogether, these results demonstrated that 9F7-F11 induced USP8 recruitment to stabilize ITCH, and then, the USP8-ITCH complex binds to the ITCH targets c-FLIP L and HER3, allowing their ubiquitination and proteasomal degradation."
USP8 binds ITCH and CFLAR. 1 / 1
| 1

sparser
"USP8-regulated ITCH binding to c-FLIP mediates c-FLIP ubiquitination in cancer cells incubated with 9F7-F11."
USP8 deubiquitinates ITCH.
1 | 1
USP8 deubiquitinates ITCH. 2 / 2
1 | 1

reach
"USP8 and USP9X deubiquitinate ITCH to induce ubiquitination and degradation of the anti-apoptotic protein c-FLIP, leading to apoptosis in glioblastoma [XREF_BIBR], or to anoikis in pancreatic ductal adenocarcinoma [XREF_BIBR]."
USP8 activates ITCH.
| 2
USP8 activates ITCH. 2 / 2
| 2

reach
"One study showed that USP8 acts downstream of PTEN to enhance the ability of the E3 ligase Itch to reduce cFLIP stability and increase tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in human glioblastoma multiforme cells [97]."

reach
"ITCH and AIP4 activity was activated by the deubiquitinases USP8 and USP9X, as demonstrated by RNA interference."
USP8 affects FLIP
| 8
USP8 decreases the amount of FLIP.
| 3
Modified USP8 decreases the amount of FLIP. 3 / 3
| 3

reach
"Overexpression of USP8 increased c-FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance (XREF_FIG)."

reach
"Over-expression of WT USP8, but not catalytically inactive USP8, increased FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance, while siRNA mediated suppression of USP8 levels had the opposite effects."

reach
"Furthermore, the suppression of FLIP S levels by USP8 over-expression was reversed by introduction of siRNA targeting AIP4."
USP8 activates FLIP.
| 2
USP8 activates FLIP. 2 / 2
| 2

reach
"Loss of PTEN function (right panel, XREF_FIG), in contrast increases pAkt levels, decreases USP8 levels, and turns off the USP8 and AIP4 ubiquitin switch, allowing FLIP S to accumulate and suppress TRAIL induced apoptosis."

reach
"Because PTEN dependent regulation of FLIP S stability is mediated by changes in FLIP S ubiquitination, we took the above USP8 modulated cells, transiently transfected a construct encoding HA tagged ubiquitin, and following FLIP S immunoprecipitation used Western blot analysis to monitor the effect of USP8 alteration on the extent of HA-ubiquitin incorporated into FLIP S."
USP8 ubiquitinates FLIP.
| 1
Modified USP8 leads to the ubiquitination of FLIP. 1 / 1
| 1

reach
"Over-expression of WT USP8, but not catalytically inactive USP8, increased FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance, while siRNA mediated suppression of USP8 levels had the opposite effects."
USP8 inhibits FLIP.
| 1
USP8 inhibits FLIP. 1 / 1
| 1

reach
"Taken together, our data indicate that USP8 functions as a novel deubiquitylase of FLIP L and inhibits extrinsic apoptosis by stabilizing FLIP L."
USP8 deubiquitinates FLIP.
| 1
USP8 deubiquitinates FLIP. 1 / 1
| 1

reach
"USP8 directly deubiquitylates and stabilizes FLIP L, but not the short isoform."
| 1 7
| 1 7

reach
"Ectopic expression of USP8 promotes ESCC tumorigenesis by suppressing ID1 degradation, whereas knockdown of USP8 results in the opposite phenotypes in vitro and in vivo."

reach
"Moreover, we found that TXNIP is a novel downstream target of ID1, and USP8 promotes ESCC tumorigenesis by activating the ID1-TXNIP pathway."

eidos
"Moreover , we found that TXNIP is a novel downstream target of ID1 , and USP8 promotes ESCC tumorigenesis by activating the ID1-TXNIP pathway ."

reach
"Present findings support that USP8 gene expression levels may contribute to pitutary tumorigenesis and hormonogenesis.."

reach
"USP8 positively regulates hepatocellular carcinoma tumorigenesis and confers ferroptosis resistance through β-catenin stabilization."

reach
"Deubiquitinase USP8 increases ID1 stability and promotes esophageal squamous cell carcinoma tumorigenesis."

reach
"The data of Kasahara et al. [88] also point to a reciprocal relationship between primary cilia and cell proliferation which may provide further insights into mechanisms of tumorigenesis caused by dysregulated USP8."

reach
"Intriguingly, GLI1 is the downstream target of sonic hedgehog (SHH) signaling that is deregulated in corticotroph tumors [57] indicating that both USP8 and USP48 might trigger corticotroph tumorigenesis via the same pathway."
USP8 affects CLOCK
| 7 1
USP8 deubiquitinates CLOCK.
| 5
USP8 deubiquitinates CLOCK. 5 / 5
| 5

reach
"As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK and CYC transcriptional activity."

reach
"Since deubiquitylation of CLK by USP8 decreases its activity XREF_BIBR, it will be interesting to investigate whether CK2alpha phosphorylation affects CLK ubiquitylation."

reach
"CLK deubiquitylation by USP8 reinforces transcriptional repression by PER complexes, whereas CLK ubiquitylation and decreased phosphorylation may be involved in shifting CLK to a transcriptionally active state."

reach
"This rhythm in ubiquitylation is mediated by UBIQUITIN SPECIFIC PROTEASE 8 (USP8), which deubiquitylates CLK to downregulate CLK-CYC activity from ~ ZT18-ZT4, thereby reinforcing PER dependent repression [XREF_BIBR]."

reach
"CLOCK deubiquitylation by USP8 inhibits CLK and CYC transcription in Drosophila."
USP8 binds CLOCK.
| 1 1
| 1 1

sparser
"As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK/CYC transcriptional activity."

reach
"As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK and CYC transcriptional activity."
USP8 decreases the amount of CLOCK.
| 1
USP8 decreases the amount of CLOCK. 1 / 1
| 1

reach
"CLOCK deubiquitylation by USP8 inhibits CLK and CYC transcription in Drosophila."
USP8 affects AKT
| 7 1
USP8 activates AKT.
| 3
USP8 activates AKT. 3 / 3
| 3

reach
"Importantly, knockdown of USP8 inhibited activation of the Akt signaling pathway by decreasing the phosphorylation level of Akt and up-regulated p53 expression, while USP8 overexpression increased activation of the Akt signaling pathway in Hucct-1 cells."

reach
"USP8 activity thus modulates VEGF-A-stimulated Akt and ERK1/2 activation but does not affect other VEGFR2 associated signal transduction pathways."

reach
"The results showed that USP8 knockdown inhibited the ratio of p-AKT/AKT in A549 and H1299 cells (Figure 4B)."
USP8 inhibits AKT.
| 2
USP8 inhibits AKT. 2 / 2
| 2

reach
"Whereas ERK1/2 and Akt signaling is inhibited by USP8 depletion, other signal transduction pathways are unaffected."

reach
"These results demonstrated that knockdown of USP8 promoted cell apoptosis of lung cancer cells by regulating the PI3K/AKT pathway."
USP8 increases the amount of AKT.
| 2
USP8 increases the amount of phosphorylated AKT. 2 / 2
| 2

reach
"Knockdown of USP8 down-regulated the expression level of p-AKT, indicating that USP8 knockdown inhibited the cell proliferation by inhibiting the PI3K/AKT pathway."

reach
"The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax."
USP8 binds AKT.
| 1
| 1

sparser
"Collectively, there may be a degenerative feedback loop of USP8-Akt ( xref ), and the Akt signaling pathway may be involved in the tumor-promoting effects of USP8 in cholangiocarcinoma."
TMEM79 affects USP8
| 8
| 6

sparser
"It seems conceivable that the Tmem79-Usp8 pair may have a primordial function in Wnt/FZD signaling in pre-bilaterians ( xref ; xref ), and that the pair have experienced losses in protostomes related to the loss of Wnt and Wnt antagonist genes."

sparser
"TMEM79 is associated with USP8 and inhibits its deubiquitination of FZD."

sparser
"Conversely TMEM79-USP8 interaction was unaffected in FZD null cells in which all 10 FZD genes have been deleted ( xref ; xref ), and is thus not mediated by FZDs."

sparser
"Investigations in cnidarians and basal protostomes will help to address the origin of Tmem79-Usp8 specificity in Wnt/FZD signaling."

sparser
"We therefore investigated TMEM79-USP8 biochemical and functional relationships."

sparser
"We further performed a phylogenic analysis of the Usp8 gene given the Tmem79-Usp8 relationship we uncovered."
FZD binds USP8 and TMEM79. 2 / 2
| 2

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"These data together suggest that the assembly of the FZD-USP8-TMEM79 complex, in which USP8 action on FZD is inhibited specifically, probably is multivalent in nature and involves additional proteins yet to be identified."
YWHAE affects USP8
5 |
5 |

No evidence text available

No evidence text available

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Ubiquitin affects USP8
| 3 3
Ubiquitin binds USP8.
| 1 3
| 1 1

sparser
"Interestingly, the crystal structure of USP8-Ubv complex shows a significantly different mode of binding than USP8-UB, suggesting phage selection using the Ubv library could find alternative binding modes with DUBs that maximize binding affinity. xref and xref also generated Ubvs for binding to DUBs of various families as well as viral DUBs."

reach
"Although there is no structure available of a USP8 and ubiquitin complex, the closely related USP domain of USP2 has been solved in the presence of ubiquitin XREF_BIBR."

sparser
"We demonstrate that the pivotal β-cell mitophagy regulator, CLEC16A, is an E3 ligase that forms a ubiquitin-dependent tripartite complex with RNF41/NRDP1 and USP8."
| 1

sparser
"There was evidence that Magel2 was involved in the leptin-POMC of the hypothalamus to maintain the energy balance of the body.[ xref ]Wijesuriya et al have found that MAGEL2 and Necdin connected leptin receptor (LepR) to the USP8-RNF41 ubiquitin complex through the LepR adapter protein, IRS4."
Ubiquitin inhibits USP8.
| 2
| 2

reach
"When we overexpressed Usp8 in ESCs, the ubiquitin modification of EPG5 decreased, while reduced Usp8 expression increased EPG5 ubiquitination (Fig. 5a, b)."

reach
"These data indicate that under ischemic conditions, Nrdp1 upregulation may hinder the stabilization of HIF-1alpha in neurons via promoting ubiquitin mediated degradation of USP8, thus attenuating cellular adaptive response to hypoxia and ischemia."
| 7
| 7

reach
"Silencing of USP8 suppresses PCa cell migration and promotes docetaxel activity."

reach
"Similarly, in PC3, silencing of USP8 was found to have significantly reduced cell migration rates at 20.6 ± 2.0%, 34.1 ± 2.7%, and 71.0 ± 2.5% compared to control at 34.9 ± 2.1%, 65.7 ± 2.6%, and 95.3 ± 2.3% over 24, 48, and 48 h, respectively ( Figures 2A2, B2 )."

reach
"Therefore, similar to the wound healing assay, it could be stated that USP8 overexpression increased the PCa cell migration and diminished the effect of docetaxel on PCa migration."

reach
"Its overexpression increased the PCa cell migration and diminished the healing action of docetaxel in both cells.Similar to the wound healing assay, overexpression of USP8 resulted in the highest number of migrated cells for both Du145 and PC3 cells in the Transwell assay, which showed statistical significance compared to all other treatment group cells ( Figure 3B )."

reach
"Finally, we show that knockdown of USP8 in human breast cancer cells suppresses cell migration."

reach
"In DU145, silencing of USP8 was found to have significantly reduced cell migration rates 16.8 ± 1.5%, 24.3 ± 2.6%, and 46.2 ± 1.4% compared to control with 28.6 ± 1.9%, 54.8 ± 3.2%, and 80.6 ± 3.7% at 24, 48, and 48 h, respectively ( Figures 2A1, B1 )."

reach
"Overexpression of USP8 promotes PCa cell migration and diminished docetaxel activity."
USP8 affects cell cycle
| 2 5
USP8 activates cell cycle.
| 1 4
| 1 4

reach
"These results indicated that knockdown of USP8 arrested the cell cycle progression from G1-phase to S-phase."

reach
"These data clearly indicate that USP8 depletion induces the loss of trichoplein and causes the ciliogenesis dependent cell cycle arrest."

eidos
"USP8 knockdown markedly induced apoptosis and cell cycle arrest ( G 0 / G 1 ) ."

reach
"These results indicated that knockdown of USP8 arrested the cell cycle progression, thereby inhibiting cell proliferation."

reach
"Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis."
USP8 inhibits cell cycle.
| 1 1
| 1 1

eidos
"Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha ."

reach
"Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis."
USP8 affects autophagy
| 1 4 1
USP8 activates autophagy.
| 3 1
| 3 1

reach
"These data indicate that USP8 guards autophagic flux in ESCs.EPG5 mediates autophagy by direct binding to LC3 using its LIR motif , which is conserved in eukaryotes (Fig. 6e)."

sparser
"We show here that UBPY silencing also activates autophagy in absence of CCCP treatment, which strongly suggests that UBPY is not connected exclusively to mitophagy."

reach
"Inactivation of human UBPY in HeLa cells activates autophagy."

reach
"Lastly, we have shown that shRNA mediated inactivation of UBPY in HeLa cells also affects autophagy which appears to be deregulated with an increased number of autophagosomes and increased autophagy flux."
USP8 inhibits autophagy.
| 1 1
| 1 1

reach
"We show here that UBPY silencing also activates autophagy in absence of CCCP treatment, which strongly suggests that UBPY is not connected exclusively to mitophagy."

eidos
"USP8 inhibitor , DUB-IN-1 , treatment could inhibit esophageal squamous cell carcinoma cell growth and induce G2 / M cell cycle arrest , apoptosis , and autophagy by DNA damage-induced p53 activation ."
USP8 affects YWHAE
5 |
5 |

No evidence text available

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USP8 affects PTPN23
1 | 4 1
1 | 4 1

No evidence text available

reach
"Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III."

reach
"Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction (s) between UBPY and HD-PTP."

sparser
"Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction(s) between UBPY and HD-PTP."

reach
"Hence, like STAM2, UBPY may bind HD-PTP at multiple sites."

reach
"We investigated in more detail how UBPY bound HD-PTP Bro1-V."
USP8 affects GC
| 7
USP8 inhibits GC.
| 5
USP8 inhibits GC. 5 / 5
| 5

reach
"We also observed that down-regulation of USP8 inhibited the proliferation of GC cells which highly expressed HER-3."

reach
"The USP8 inhibited HER-2 positive GC cell proliferation and migration in vivo and in vitro and probably served as a novel potential therapeutic biomarker for HER-2 positive GC."

reach
"XREF_BIBR, XREF_BIBR Therefore, it can be inferred that down-regulation of USP8 may inhibit the proliferation and even metastasis of GC through this pathway."

reach
"In order to find out whether the pharmacological inactivation of USP8 could inhibit the growth of GC cells and was related to HER-3, USP8 inhibitor (DUBs-IN-2, XREF_FIG) was applied to evaluate the antiproliferation activity in these cell lines in XREF_FIG."

reach
"All in vitro results demonstrated that down-regulation of USP8 inhibited the proliferation and viability of GC cells with high expression of HER3 (NCI-N87, MKN-45 and AGS), but did not affect HER3 negative cells (MGC-803)."
USP8 activates GC.
| 2
USP8 activates GC. 2 / 2
| 2

reach
"These results indicated that down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle."

reach
"Moreover, down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle."
STAMBP affects STAM
| 7
STAM binds USP8 and STAMBP. 5 / 5
| 5

sparser
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner ( xref )."

sparser
"The functional relevance of the interaction between USP8, AMSH, and STAM in the endocytic trafficking of activated growth factors is supported by other observations, including that catalytically inactive AMSH, a potential “substrate trap” mutant, resulted in the accumulation of ubiquitin on endosomes, an increased association with STAM, and the generation of a minor product consistent with ubiquitylated STAM ( xref )."

sparser
"This also contains the sequence PPPRPTAPKP, which binds the Mona SH3 domain [ 39 ] and closely resembles the PXXXRXXKP motifs in UBPY [ 21, 28 ] and AMSH [ 20 ] that bind STAM SH3."

sparser
"AMSH (a JAMM family member with specificity for K63 chains) and USP8 associate with STAM proteins, a component of the ESCRT-0 complex xref , xref ."

sparser
"Both AMSH and Usp8 bind to ESCRT-0 protein STAM through a non-canonical SH3-binding motif, and with their MIT-domain to several CHMP proteins of the ESCRT-III machinery [30,37,39,40] ."
STAM binds USP8, STAMBP, and HRS. 1 / 1
| 1

sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
PTPN23 affects USP8
1 | 4 1
1 | 4 1

No evidence text available

reach
"Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III."

reach
"Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction (s) between UBPY and HD-PTP."

sparser
"Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction(s) between UBPY and HD-PTP."

reach
"Hence, like STAM2, UBPY may bind HD-PTP at multiple sites."

reach
"We investigated in more detail how UBPY bound HD-PTP Bro1-V."
USP8 affects UBC
6 |
6 |

No evidence text available

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USP8 affects SNCA
3 2 | 1
USP8 binds SNCA.
3 | 1
3 | 1

No evidence text available

No evidence text available

sparser
"USP8 interacts with α-synuclein and cleaves Lys63 ubiquitin chains in α-synuclein, thereby inhibiting α-synuclein degradation in the lysosome xref ."

No evidence text available
USP8 deubiquitinates SNCA.
2 |
USP8 deubiquitinates SNCA. 2 / 2
2 |

"In addition, this study identifies USP8 as one of the best markers of Lewy bodies in human pigmented neurons in sporadic cases of Parkinson’s disease and demonstrates the ability of USP8 to hydrolyze K63-linked ubiquitin chains from α-synuclein in vitro"

"Another deubiquitinase, USP8, removes K63-linked ubiquitin chains of α-synuclein and prevents its lysosomal degradation."
USP8 affects KCNN4
1 1 | 3 1
USP8 deubiquitinates KCNN4.
1 | 2
USP8 deubiquitinates KCNN4. 3 / 3
1 | 2

reach
"Further, we demonstrated that KCa3.1 is initially ubiquitylated following endocytosis and then deubiquitylated by USP8 prior to lysosomal degradation XREF_BIBR."

reach
"Further, overexpression of wild-type USP8 accelerates channel deubiquitylation, while either a catalytically inactive mutant USP8 or siRNA mediated knockdown of USP8 enhanced accumulation of ubiquitylated KCa3.1, thereby inhibiting channel degradation."
USP8 binds KCNN4.
1 | 1 1
1 | 1

No evidence text available

reach
"Using the DUB Chip, a protein microarray containing 35 DUBs, we demonstrate a time dependent association between KCa3.1 and USP8 following endocytosis, which was confirmed by coimmunoprecipitation."
USP2 binds USP8 and KCNN4. 1 / 1
| 1

sparser
"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."
USP8 affects EPS15
2 1 | 3
USP8 deubiquitinates EPS15.
1 | 1
USP8 deubiquitinates EPS15. 2 / 2
1 | 1

reach
"UBPY also deubiquitinated Eps15 in vitro, suggesting that Eps15 is a cellular substrate for UBPY."

No evidence text available
USP8 binds EPS15.
2 |
2 |

No evidence text available

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USP8 activates EPS15.
| 2
USP8 activates EPS15. 2 / 2
| 2

reach
"Furthermore, inactivation of UBPY caused the accumulation of Eps15 on the endosomal aggregates."

reach
"Another DUB enzyme, USP8, functions similarly to target Eps15 [XREF_BIBR]."
UBC affects USP8
6 |
6 |

No evidence text available

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OTUB1 affects USP8
1 | 2 3
OTUB1 inhibits USP8.
| 2 1
OTUB1 inhibits USP8. 3 / 3
| 2 1

sparser
"This unexpected function of otubain-1 might be mediated through the inhibition of USP8, a DUB that binds to and deubiquitylates GRAIL; however, it is not known how otubain-1 might inhibit USP8 (Ref. xref )."

reach
"This unexpected function of otubain-1 might be mediated through the inhibition of USP8, a DUB that binds to and deubiquitylates GRAIL; however, it is not known how otubain-1 might inhibit USP8."

reach
"Interestingly, Otub1 expression completely abolished USP8 mediated stabilization of GRAIL when all 3 proteins were co-expressed."
OTUB1 binds USP8.
1 | 2
1 | 2

sparser
"Otub1 forms a trimolecular complex with USP8 and GRAIL, and upregulated Otub1 promotes GRAIL's proteosomal degradation."

sparser
"USP8 can form a complex with RNF128 and OTUB1 to regulate the anergy of T-cells mediated by RNF128 ( xref )."

No evidence text available
ERBB2 affects USP8
| 1 3
ERBB2 binds USP8.
| 3
| 3

sparser
"Our current findings further demonstrate that Usp8 binds to ErbB2 and that Usp8 tyrosine phosphorylation is dependent on ErbB2- ( Fig. 4 ) and Src- kinase ( Fig. 5 ) activities, thereby extending our [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Given the impaired downregulation of ErbB2, we have investigated in the present study whether ErbB2 and Usp8 functionally interact."

sparser
"Moreover, we show that Usp8 interacts with ErbB2 and is tyrosine phosphorylated in a ErbB2- and Src kinase-dependent manner, although its tyrosine phosphorylation is to a lesser extent than in the cas[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
ERBB2 phosphorylates USP8.
| 1
ERBB2 leads to the phosphorylation of USP8 on tyrosine. 1 / 1
| 1

reach
"This model is supported by our current findings that TGFalpha stimulation of EGFR and EGF stimulation of ERBB2 [52], conditions that are associated with enhanced endosomal recycling and decreased MVB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
CFLAR affects USP8
4 | 2
4 | 1

sparser
"However, Jeong et al. [ xref ] showed that USP8 directly interacts with the caspase-like domain in c-FLIP L to induce deubiquitination and stabilization of cFLIP L , but not cFLIP S . Depletion of USP8 destabilized cFLIP L resulting in sensitization to DR-induced apoptosis."

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP8 binds ITCH and CFLAR. 1 / 1
| 1

sparser
"USP8-regulated ITCH binding to c-FLIP mediates c-FLIP ubiquitination in cancer cells incubated with 9F7-F11."
BRIT1 affects USP8
| 6
USP8 binds BIRC6 and BRIT1. 6 / 6
| 6

reach
"Given the fact that the integrity of the BRUCE, USP8, and BRIT1 complex is essential for targeting BRIT1 to DSB, whether the observed UBC requirement is attributable to its contribution to maintaining the complex integrity was examined."

reach
"Mutation or deletion of the BRUCE UBC domain did not disrupt the BRUCE, USP8, and BRIT1 complex, but impaired deubiquitination and consequent recruitment of BRIT1 to DSB."

reach
"Once deubiquitinated, BRIT1 is released from the BRUCE, USP8, and BRIT1 complex and targeted to DSBs by binding to gamma-H2AX at sites of DSB [XREF_BIBR], where BRIT1 recruits the SWI/SNF chromatin remodeling complex to facilitate relaxation of chromatin configuration for the access of repair factors to damaged chromatin [XREF_BIBR]."

reach
"The formation of the BRUCE, USP8, and BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

reach
"This deubiquitination triggers the release of BRIT1 from the BRUCE, USP8, and BRIT1 complex and consequently released BRIT acquires the ability to be recruited to sites of DNA damage by binding to phosphorylated H2AX (gamma-H2AX)."

reach
"Together, these results indicate that subsequent to the formation of the BRUCE, USP8, and BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
AKT affects USP8
| 4 1
AKT inhibits USP8.
| 1
AKT inhibits USP8. 1 / 2
| 1

reach
"In the present study the linkage between PTEN loss, Akt activation, and USP8 levels and activity appeared to be somewhat different, and in our work Akt activation decreased, rather than enhanced, USP8 function by increasing USP8 ubiquitination and decreasing steady-state USP8 levels (data not shown)."
AKT activates USP8.
| 2
AKT activates USP8. 2 / 2
| 2

reach
"In addition to suppressing levels of USP8, Akt may also stimulate the activity of USP8 toward select targets such as Nrdp1."

reach
"Hyperactivation of AKT in LUAD promotes the combination of USP8 and stratifin (SFN)."
AKT deubiquitinates USP8.
| 1
AKT leads to the deubiquitination of USP8. 1 / 1
| 1

reach
"The AKT kinase has been previously shown to decrease USP8 function by increasing USP8 ubiquitination and decreasing active steady-state USP8 level [XREF_BIBR]."
AKT binds USP8.
| 1
| 1

sparser
"Collectively, there may be a degenerative feedback loop of USP8-Akt ( xref ), and the Akt signaling pathway may be involved in the tumor-promoting effects of USP8 in cholangiocarcinoma."
YWHAQ affects USP8
4 1 |
4 1 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP8 affects localization
| 5
USP8 inhibits localization.
| 3
| 3

reach
"Moreover, we found that USP8 prevents Smo localization to early endosomes that are labeled with Rab5."

reach
"However, in the case of USP8, phosphorylation at Ser680 is also critical for its subcellular localization since mutation of Ser680 to Ala restricts its localization to the nucleus, whereas the wild type is predominantly localized into the cytosol essential for USP8 interaction with the protein 14-3-3ε [57]."

reach
"USP8 Prevents the Localization of Smo to the Early Endosome."
USP8 activates localization.
| 2
| 2

reach
"Moreover, Shi RNAi attenuated the localization of Smo in the early endosomes (XREF_FIG), whereas USP8 RNAi elevated the localization (XREF_FIG)."

reach
"Catalytic inactivation of USP8 incurs EGFR hyperubiquitination and promotes receptor localization to endosomes marked by high ubiquitin content."
| 3

reach
"USP8 treatment improved cognitive dysfunction and inhibited inflammation and oxidative stress in CLP mice."

reach
"An earlier study by Zhang et al. showed that USP8, through deubiquitination and inactivation of TAK1, suppressed intermittent hypoxia/reoxygenation-induced inflammation in renal tubular epithelial cells [16]."

reach
"In conclusion, USP8 inhibited lipopolysaccharide-triggered inflammation and pyroptosis in human bronchial epithelial cells by activating PI3K/AKT signaling and inhibiting NF-κB signaling pathway."
| 2

reach
"The present study is the first, to the best of our knowledge, to investigate the effects of ubiquitin specific peptidase 8 (USP8) on IHR induced inflammation in renal tubular epithelial cells and examine the underlying mechanism."

reach
"Effect of deubiquitinase USP8 on hypoxia and reoxygenation induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells."
USP8 affects gefitinib
| 5
USP8 activates gefitinib.
| 3
| 3

reach
"Interestingly, the inhibition of USP8 suppresses growth of gefitinib resistant non small cell lung cancer cells, though no link to the potential impact on HIF-1alpha is reported."

reach
"Silencing or pharmacological inhibition of USP8 deubiquitinase, relevant in particular to the stability of RTKs such as EGFR and MET, was shown to induce death of gefitinib resistant NSCLC cells in vitro and in vivo [XREF_BIBR]."

reach
"In addition, studies have shown that USP8 knockdown or inhibitors can significantly reduce the viability of gefitinib-resistant and -sensitive NSCLC cells by reducing the expression of receptor tyrosine kinase (RTK).14,15Baykara et al find that the serum USP8 level in NSCLC patients was higher than in healthy individuals."
USP8 inhibits gefitinib.
| 2
| 2

reach
"Downregulation of USP8 inhibits the survival of gefitinib-resistant non-small cell lung cancer (NSCLC) cells."

reach
"Knock-down of USP8 selectively decreases viability of gefitinib resistant NSCLC cells."
USP8 affects degradation
| 5
USP8 inhibits degradation. 5 / 5
| 5

sparser
"Finally, USP8 inhibited SQSTM1 degradation and autophagic influx in cells with wild-type SQSTM1, but not its mutant with substitution of K420 with an arginine."

sparser
"USP8 or USP9X silencing inhibits ITCH-mediated HER3 degradation induced by the anti-HER3 antibody 9F7-F11."

sparser
"While one report suggests that Usp8 inhibits EGFR degradation [25] , we and others have demonstrated that Usp8 promotes EGFR degradation [21,26] ."

sparser
"Although EGFR overexpression is not a consistent finding in USP8 mutation positive tumors, in vitro studies have proven that USP8 mutants inhibit the degradation of the ligand-bound EGFR in EGF-stimulated cells. xref , xref Expression of the somatostatin receptor type 5 (SSTR5) and O-6-methylguanine-DNA methyltransferase (MGMT) are increased in USP8 -mutated tumors, suggesting that such tumors might be responsive to the pharmacological treatment with pasireotide, but not with temozolomide. xref The frequency of USP8 mutations is higher in females in all the cohorts reported so far, but there are discrepancies among studies regarding other clinical and biochemical features. xref – xref , xref Interestingly, the frequency of USP8 mutations in a recently reported cohort of patients with Nelson’s syndrome (45%), was not higher than what has been reported for CD, although such mutations were associated with lower frequency of ACTH normalization after surgery. xref "

sparser
"While some reports suggest that Usp8 inhibits EGFR degradation [40] , we and others demonstrated that Usp8 stimulates EGFR degradation [41,42] ."
USP8 affects YWHAQ
4 1 |
4 1 |

No evidence text available

No evidence text available

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USP8 affects RACK1
| 1 4
SMO binds USP8 and RACK1. 3 / 3
| 3

sparser
"In the presence of Hh, Hh dissociates Ci–Rack1 interaction, and promotes Rack1 forming a trimeric complex with Usp8 and Smo, resulting in Smo deubiquitination and cell surface accumulation (Fig.  xref )."

sparser
"The two-step co-IP assay showed that Usp8, Rack1, and Smo formed a trimeric complex (Fig.  xref )."

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
| 1 1

sparser
"Through biochemical analyses, we find that Rack1 binds Smo and recruits the deubiquitinase Usp8, which is boosted by Hh stimulation."

reach
"Through biochemical analyses, we find that Rack1 binds Smo and recruits the deubiquitinase Usp8, which is boosted by Hh stimulation."
USP8 affects NTRK2
| 1 2 2
USP8 deubiquitinates NTRK2.
| 1 2
USP8 deubiquitinates NTRK2. 3 / 3
| 1 2

reach
"TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation."

reach
"TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation."

trips
"TrkB deubiquitination by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation."
USP8 binds NTRK2.
| 2
| 2

sparser
"USP8 binds to the C-terminus of TrkB using its microtubule interacting domain (MIT)."

sparser
"USP8 binds to the C-terminus of TrkB using its microtubule interacting domain (MIT)."
USP8 affects FZD
| 5
| 3

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"FZD-USP8 interaction was unaffected by TMEM79 overexpression ( xref ), ruling out a scenario that TMEM79 competes with FZD for USP8-binding to achieve inhibition of FZD deubiquitination by USP8."

sparser
"We found that FZD-USP8 interaction was observed in TMEM79 KO cells ( xref ) and thus is not mediated by TMEM79."
FZD binds USP8 and TMEM79. 2 / 2
| 2

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"These data together suggest that the assembly of the FZD-USP8-TMEM79 complex, in which USP8 action on FZD is inhibited specifically, probably is multivalent in nature and involves additional proteins yet to be identified."
USP8 affects E3_Ub_ligase
| 3 2
| 1 2

sparser
"We demonstrate that the pivotal β-cell mitophagy regulator, CLEC16A, is an E3 ligase that forms a ubiquitin-dependent tripartite complex with RNF41/NRDP1 and USP8."

sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."

reach
"USP8 interacts with AIP4 and retains this E3 ubiquitin ligase in a state in which it can interact with FLIP S."
USP8 activates E3_Ub_ligase.
| 2
| 2

reach
"One study showed that USP8 acts downstream of PTEN to enhance the ability of the E3 ligase Itch to reduce cFLIP stability and increase tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in human glioblastoma multiforme cells [97]."

reach
"Ubiquitin-specific protease 8 (USP8) belongs to ubiquitin proteasome system and mediates the stability of E3 ligases."
USP8 affects CHMP4B
| 3 2
| 3 2

sparser
"Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction(s) between UBPY and HD-PTP."

reach
"In a sequence of competitive interactions, STAM2, which binds to HD-PTP/PTPN23 via two interactions, is replaced by CHMP4B and USP8 binding to both STAM2 and HD-PTP/PTPN23."

sparser
"We investigated in more detail how UBPY bound HD-PTP Bro1-V. We focused on the N-terminal MIT domain of UBPY, which also binds CHMP4B, because this is essential for recruiting UBPY to endosomes and su[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"First, the coordinated recruitment of CHMP4B and UBPY to HD-PTP would bring about exchange reactions that disrupt both modes of STAM2 binding to HD-PTP."

reach
"Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III."
USP8 affects ARL6IP4
| 5
USP8 binds ARL6IP4.
| 3
| 3

reach
"USP8 interacts with AIP4 and retains this E3 ubiquitin ligase in a state in which it can interact with FLIP S."

reach
"Collectively, our findings demonstrate a functional cooperation between USP8, AIP4, and the ESCRT-0 machinery at the early sorting phase of CXCR4 and underscore the versatility of USP8 in shaping trafficking events at the early-to-late endosome transition."

reach
"A direct interaction between USP8 and AIP4 has not been reported, and it is possible that instead of directly deubiquitinating AIP4, USP8 may alter the ability of other E3 ligases (or perhaps of AIP4 itself) to stimulate AIP4 K63 polyubiquitination."
USP8 deubiquitinates ARL6IP4.
| 2
USP8 leads to the deubiquitination of ARL6IP4. 2 / 2
| 2

reach
"Consistent with this idea, overexpression of wild-type USP8 decreased the ubiquitination of the FLIP (S) E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP (S) interaction, whereas siRNA mediated suppression of USP8 increased AIP4 ubiquitination."

reach
"Consistent with this idea, over-expression of WT USP8 decreased ubiquitination of the FLIP S E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP S interaction, while siRNA mediated suppression of USP8 increased AIP4 ubiquitination."
TARDBP affects USP8
3 2 |
3 2 |

No evidence text available

"The ubiquitin-conjugating enzyme UBE2E3 and ubiquitin-isopeptidase Y (UBPY) were identified, in a yeast two-hybrid screen, to interact with TDP-43 and this interaction is proposed to enhance the ubiquitination and accumulation of its insoluble high molecular weight aggregates (Hans et al., 2014)."

No evidence text available

No evidence text available

"The ubiquitin-conjugating enzyme UBE2E3 and ubiquitin-isopeptidase Y (UBPY) were identified, in a yeast two-hybrid screen, to interact with TDP-43 and this interaction is proposed to enhance the ubiquitination and accumulation of its insoluble high molecular weight aggregates (Hans et al., 2014)."
STAM affects STAMBP, and USP8
| 5
STAM binds USP8 and STAMBP. 5 / 5
| 5

sparser
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner ( xref )."

sparser
"The functional relevance of the interaction between USP8, AMSH, and STAM in the endocytic trafficking of activated growth factors is supported by other observations, including that catalytically inactive AMSH, a potential “substrate trap” mutant, resulted in the accumulation of ubiquitin on endosomes, an increased association with STAM, and the generation of a minor product consistent with ubiquitylated STAM ( xref )."

sparser
"This also contains the sequence PPPRPTAPKP, which binds the Mona SH3 domain [ 39 ] and closely resembles the PXXXRXXKP motifs in UBPY [ 21, 28 ] and AMSH [ 20 ] that bind STAM SH3."

sparser
"AMSH (a JAMM family member with specificity for K63 chains) and USP8 associate with STAM proteins, a component of the ESCRT-0 complex xref , xref ."

sparser
"Both AMSH and Usp8 bind to ESCRT-0 protein STAM through a non-canonical SH3-binding motif, and with their MIT-domain to several CHMP proteins of the ESCRT-III machinery [30,37,39,40] ."
RACK1 affects USP8
| 1 4
SMO binds USP8 and RACK1. 3 / 3
| 3

sparser
"In the presence of Hh, Hh dissociates Ci–Rack1 interaction, and promotes Rack1 forming a trimeric complex with Usp8 and Smo, resulting in Smo deubiquitination and cell surface accumulation (Fig.  xref )."

sparser
"The two-step co-IP assay showed that Usp8, Rack1, and Smo formed a trimeric complex (Fig.  xref )."

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
| 1 1

sparser
"Through biochemical analyses, we find that Rack1 binds Smo and recruits the deubiquitinase Usp8, which is boosted by Hh stimulation."

reach
"Through biochemical analyses, we find that Rack1 binds Smo and recruits the deubiquitinase Usp8, which is boosted by Hh stimulation."
MCPH1 affects BIRC6
| 5
USP8 binds BIRC6 and MCPH1. 5 / 5
| 5

sparser
"Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex."

sparser
"Specifically, the BIR is dispensible for the scaffold function of BRUCE in tethering USP8 and BRIT1 forming the nuclear BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"The formation of the BRUCE-USP8-BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

sparser
"In the recently elucidated role of BRUCE in the regulation of DNA damage signaling and repair, neither the BIR or UBC is required for the scaffold function of BRUCE in the formation of BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"Together, these results indicate that subsequent to the formation of the BRUCE-USP8-BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
Hedgehog affects USP8
| 2
Hedgehog activates USP8. 2 / 5
| 2

reach
"CFP-Smo was transfected into S2 cells that were treated with GFP dsRNA (control), USP8 dsRNA, or Shi dsRNA and then treated with Hh conditioned medium or control medium."

reach
"Mechanistically, we show that Hh promotes the interaction of USP8 with Smo aa625-753, which covers the three PKA and CK1 phosphorylation clusters."
FZD affects USP8
| 5
| 3

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"FZD-USP8 interaction was unaffected by TMEM79 overexpression ( xref ), ruling out a scenario that TMEM79 competes with FZD for USP8-binding to achieve inhibition of FZD deubiquitination by USP8."

sparser
"We found that FZD-USP8 interaction was observed in TMEM79 KO cells ( xref ) and thus is not mediated by TMEM79."
FZD binds USP8 and TMEM79. 2 / 2
| 2

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"These data together suggest that the assembly of the FZD-USP8-TMEM79 complex, in which USP8 action on FZD is inhibited specifically, probably is multivalent in nature and involves additional proteins yet to be identified."
E3_Ub_ligase affects USP8
| 3 2
| 1 2

sparser
"We demonstrate that the pivotal β-cell mitophagy regulator, CLEC16A, is an E3 ligase that forms a ubiquitin-dependent tripartite complex with RNF41/NRDP1 and USP8."

sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."

reach
"USP8 interacts with AIP4 and retains this E3 ubiquitin ligase in a state in which it can interact with FLIP S."
E3_Ub_ligase ubiquitinates USP8.
| 2
E3_Ub_ligase ubiquitinates USP8. 2 / 2
| 2

reach
"Mechanistically, the E3 ligase Nrdp1 indirectly destabilizes the ESCRT-0 complex by ubiquitinating and suppressing USP8."

reach
"The cell-surface receptor Fz is ubiquitinated by the transmembrane E3 ligases ZNRF3 and RNF43 and is deubiquitinated by UBPY/Ub-specific protease 8 (USP8) for recycling to the plasma membrane (69, 70)."
CHMP4B affects USP8
| 3 2
| 3 2

sparser
"Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction(s) between UBPY and HD-PTP."

reach
"In a sequence of competitive interactions, STAM2, which binds to HD-PTP/PTPN23 via two interactions, is replaced by CHMP4B and USP8 binding to both STAM2 and HD-PTP/PTPN23."

sparser
"We investigated in more detail how UBPY bound HD-PTP Bro1-V. We focused on the N-terminal MIT domain of UBPY, which also binds CHMP4B, because this is essential for recruiting UBPY to endosomes and su[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"First, the coordinated recruitment of CHMP4B and UBPY to HD-PTP would bring about exchange reactions that disrupt both modes of STAM2 binding to HD-PTP."

reach
"Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III."
BIRC6 affects MCPH1, and USP8
| 5
USP8 binds BIRC6 and MCPH1. 5 / 5
| 5

sparser
"Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex."

sparser
"Specifically, the BIR is dispensible for the scaffold function of BRUCE in tethering USP8 and BRIT1 forming the nuclear BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"The formation of the BRUCE-USP8-BRIT1 complex in unstimulated cells is mediated by N-terminal half of BRUCE (N-BRUCE)."

sparser
"In the recently elucidated role of BRUCE in the regulation of DNA damage signaling and repair, neither the BIR or UBC is required for the scaffold function of BRUCE in the formation of BRUCE-USP8-BRIT1 complex [ xref ]."

sparser
"Together, these results indicate that subsequent to the formation of the BRUCE-USP8-BRIT1 complex mediated by N-BRUCE, the C-BRUCE is required for targeting BRIT1 to DSB sites."
YWHAB affects USP8
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP8 affects trichoplein
| 4
USP8 binds trichoplein.
| 3
USP8 binds trichoplein. 3 / 3
| 3

reach
"Pull-down assays showed that bacterially purified GST-USP8 bound trichoplein in RPE1 lysates."

reach
"Co-immunoprecipitation assays also demonstrated binding between trichoplein and FLAG-USP8."

reach
"We, therefore, tested if USP8 bound trichoplein."
USP8 activates trichoplein.
| 1
USP8 activates trichoplein. 1 / 1
| 1

reach
"It remains unclear how serum starvation terminates the USP8 mediated stabilization of trichoplein."
| 2

reach
"In conclusion, USP8 inhibited lipopolysaccharide-triggered inflammation and pyroptosis in human bronchial epithelial cells by activating PI3K/AKT signaling and inhibiting NF-κB signaling pathway."

reach
"VEGF-A-stimulated VEGFR2 signal transduction is perturbed by USP8 depletion."
| 2

reach
"The inhibition of USP8 downregulated the Notch signalling pathway via NICD destabilization, resulting in the retardation of cellular growth, wound closure, and colony forming ability of breast cancer cell lines."

reach
"Knockdown of USP8 inhibits prostate cancer cell growth, proliferation, and metastasis and promotes docetaxel's activity by suppressing the NF-kB signaling pathway."
| 1 3
USP8 inhibits cilium assembly.
| 1 1
| 1 1

eidos
"CRL3KCTD17 , USP8 , and TCHP TCHP , a centriolar protein originally identified as a keratin-binding protein , activates AURKA and suppresses ciliogenesis [ 101,141,142 ] ."
| PMC

reach
"USP8 phosphorylation on Tyr717 and Tyr810 by EGFR kinase elevates its activity and then activates an inhibitory mechanism of ciliogenesis, i.e., EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase [24]."
USP8 activates cilium assembly.
| 2

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC

reach
"In zebrafish, knockout (KO) of kctd17 impairs ciliogenesis in Kupffer’s vesicle and induces situs inversus [74], whereas KO of usp8 increases ciliogenesis in the pronephric duct and causes renal cysts [50]."
| PMC
USP8 affects YWHAB
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP8 affects Wnt
| 1 3
USP8 activates Wnt. 4 / 4
| 1 3

reach
"Thus, our study demonstrated that USP8 activated the Wnt/beta-catenin signaling through a post-translational mechanism of β-catenin."

reach
"USP8 and UBPY is reported to activate the Wnt and beta-catenin pathway by targeting Frizzled G protein coupled protein XREF_BIBR."

eidos
"USP8 enhances Wnt signaling through deubiquitinating FZD5 ."

reach
"Additionally, the deubiquitinating enzymes UBPY and USP6 may promote the recycling of endocytosed FZD back to the surface and restore Wnt signaling."
USP8 affects SQSTM1
| 4
USP8 deubiquitinates SQSTM1. 4 / 4
| 4

reach
"USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR]."

reach
"USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR]."

reach
"USP8 overexpression leads to deubiquitination of p62 protein, suppressing its autophagic activity (Peng et al. 2020)."

reach
"USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction."
USP8 affects NTRK1
1 | 2 1
1 | 2 1

sparser
"Recent studies have attempted to identify the specific DUBs associated with TrkA, where Ceriani and collaborators described an interaction between TrkA and USP8 (USP-family) in PC12 cells [ xref ]."

reach
"The deubiquitinating enzyme UBPy and USP8 interacts with TrkA and inhibits neuronal differentiation in PC12 cells."

reach
"Recent studies have attempted to identify the specific DUBs associated with TrkA, where Ceriani and collaborators described an interaction between TrkA and USP8 (USP family) in PC12 cells [XREF_BIBR]."

No evidence text available
USP8 affects NFkappaB
| 1 3
USP8 activates NFkappaB. 4 / 4
| 1 3

eidos
"Therefore , by these findings , it can be concluded that USP8 , EGFR , PI3K , and P-Akt can activate NF-kappaB signaling where USP8 is a regulator of EGFR , PI3K , and P-Akt in PCa cell proliferation and survival ."

reach
"In contrast, the USP8-specific siRNA reduced EGFR and PI3K, suppressing the NF-kB signal."

reach
"Knockdown of USP8 inhibits prostate cancer cell growth, proliferation, and metastasis and promotes docetaxel's activity by suppressing the NF-kB signaling pathway."

reach
"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."
USP8 affects Hedgehog
| 2
USP8 activates Hedgehog. 2 / 4
| 2

reach
"Loss of USP8/UBPY blocked Hh-induced Smo accumulation whereas overexpression of USP8/UBPY resulted in ectopic Smo accumulation and Hh pathway activation [42,43]."
| PMC

reach
"Although the loss-of-function of USP8 can block Hh induced cell surface accumulation of Smo, we found that USP8 only stabilizes Smo but does not regulate Smo phosphorylation in the absence of Hh (XREF_FIG), suggesting that the regulation of Smo by USP8 is downstream of Smo phosphorylation."
USP8 affects GRIA
| 4
USP8 deubiquitinates GRIA.
| 3
USP8 deubiquitinates GRIA. 3 / 3
| 3

reach
"This homeostatic mechanism is directly antagonized by NMDAR-dependent activation of the deubiquitinating enzyme ubiquitin carboxyl-terminal hydrolase 8 (USP8), to favor AMPAR deubiquitination and therefore AMPAR recycling (Scudder et al., 2014)."

reach
"Furthermore, shRNA mediated knockdown of USP8 is sufficient to enhance the basal level of AMPAR ubiquitination in primary neurons."

reach
"In addition to USP46, USP8 can also deubiquitinate mammalian AMPARs indicating that multiple regulatory mechanisms exist to control AMPAR ubiquitination levels (Scudder et al., 2014)."
USP8 ubiquitinates GRIA.
| 1
USP8 leads to the ubiquitination of GRIA. 1 / 1
| 1

reach
"This homeostatic mechanism is directly antagonized by NMDAR-dependent activation of the deubiquitinating enzyme ubiquitin carboxyl-terminal hydrolase 8 (USP8), to favor AMPAR deubiquitination and therefore AMPAR recycling (Scudder et al., 2014)."
USP8 affects GJA1
1 | 3
USP8 deubiquitinates GJA1. 4 / 4
1 | 3

reach
"USP8 reduces both multiple monoubiquitination and polyubiquitination of Cx43 to prevent autophagy mediated degradation."

"The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43"

reach
"Ectopic overexpression of USP8 was found to promote the loss of both Cx43 monoubiquitination and polyubiquitin chains linked via Lys48 or Lys63, which was associated with increased Cx43 protein levels."

reach
"USP8 interacts with and deubiquitinates Cx43, removing monoubiquitin moieties as well as K63- and K48 linked ubiquitin chains."
USP8 affects ESCRT-III
| 4
USP8 activates ESCRT-III.
| 3
USP8 activates ESCRT-III. 3 / 3
| 3

reach
"These binding reactions provide a scenario in which UBPY could aid transit of EGFR to ESCRT-III by helping to displace STAM2 from HD-PTP."

reach
"Deubiquitinating enzymes (DUBs) AMSH and UBPY targeting ESCRT-III play an important role in ESCRT regulated processes [XREF_BIBR, XREF_BIBR, XREF_BIBR] and many ESCRT-III interaction partners recognize sequence motifs located within the C-terminus of ESCRT-III family members [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."

reach
"In the present study, we describe that USP8 and UBPY also targets the ESCRT-III machinery."
USP8 binds ESCRT-III.
| 1
USP8 binds ESCRT-III. 1 / 1
| 1

reach
"In this scenario, UBPY, bound to ESCRT-III, should have sufficient reach to deubiquitinate EGFR and thus destabilise the structure, triggering ILV involution as a prelude to membrane scission."
USP8 affects CHMP1A
2 | 1 1
2 | 1

No evidence text available

reach
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

No evidence text available
| 1

sparser
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
SNCA affects USP8
3 | 1
3 | 1

No evidence text available

No evidence text available

sparser
"USP8 interacts with α-synuclein and cleaves Lys63 ubiquitin chains in α-synuclein, thereby inhibiting α-synuclein degradation in the lysosome xref ."

No evidence text available
NTRK1 affects USP8
1 | 2 1
1 | 2 1

sparser
"Recent studies have attempted to identify the specific DUBs associated with TrkA, where Ceriani and collaborators described an interaction between TrkA and USP8 (USP-family) in PC12 cells [ xref ]."

reach
"The deubiquitinating enzyme UBPy and USP8 interacts with TrkA and inhibits neuronal differentiation in PC12 cells."

reach
"Recent studies have attempted to identify the specific DUBs associated with TrkA, where Ceriani and collaborators described an interaction between TrkA and USP8 (USP family) in PC12 cells [XREF_BIBR]."

No evidence text available
ITCH affects USP8
| 4
| 3

sparser
"For the interaction of Usp8 and Itch, it has been described that the deubiquitinase Usp8 removes ubiquitin chains on the E3-ligase Itch, which increases its activity towards cFLIP S [ xref ]."

sparser
"One such example has been described for the Itch-Usp8 ‘partnership’, where Usp8 increases the activity of Itch by deubiquitination [ xref ]."

sparser
"Altogether, these results demonstrated that 9F7-F11 induced USP8 recruitment to stabilize ITCH, and then, the USP8-ITCH complex binds to the ITCH targets c-FLIP L and HER3, allowing their ubiquitination and proteasomal degradation."
USP8 binds ITCH and CFLAR. 1 / 1
| 1

sparser
"USP8-regulated ITCH binding to c-FLIP mediates c-FLIP ubiquitination in cancer cells incubated with 9F7-F11."
CHMP1A affects USP8
2 | 1 1
2 | 1

No evidence text available

reach
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

No evidence text available
| 1

sparser
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
Trichoplein affects USP8
| 3
USP8 binds trichoplein. 3 / 3
| 3

reach
"Pull-down assays showed that bacterially purified GST-USP8 bound trichoplein in RPE1 lysates."

reach
"Co-immunoprecipitation assays also demonstrated binding between trichoplein and FLAG-USP8."

reach
"We, therefore, tested if USP8 bound trichoplein."
YWHAZ affects USP8
2 | 1
2 | 1

No evidence text available

reach
"Although the affinity of UBPY for different 14-3-3 isoforms has not been compared, these observations suggest that UBPY exhibits broad binding specificity for 14-3-3 isoforms.A proteomic analysis usin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available
USP8 affects sub
| 3
USP8 activates sub. 2 / 2
| 2

reach
"These data suggest that USP8 phosphorylation, possibly on Tyr residue (s), enhances its DUB activity."

reach
"The putative substrate of BRUCE could be USP8 and if this is the case, ubiquitination of USP8 by BRUCE is expected to enhance its Dub activity over Ub-BRIT1, thereby facilitating removal of the Ub chains from K63-Ub-BRIT1 and promoting recruitment of de-ubiquitinated BRIT1 to sites of DNA damage."
USP8-S680A activates sub. 1 / 1
| 1

reach
"Furthermore, the catalytic activity of USP8 is inhibited by phosphorylation on Ser 680, based on the fact that the S680A mutant of USP8 exhibites enhanced DUB activity toward polyubiquitin chains and EGFR."

reach
"USP8 promotes TGF-β/SMAD-induced epithelial-mesenchymal transition (EMT), invasion, and metastasis in tumor cells."

reach
"Here in this study, we found that knocking down USP8 significantly inhibited the PCa cell migration by suppressing the EMT process through the increased E-cadherin and decreased N-cadherin, whereas USP8 overexpression promoted the EMT process through the decreased E-cadherin and increased N-cadherin and so thereby increased the migration of both DU145 and PC3 cells.Knocking down USP8 downregulated the NF-κB signal by decreasing its intermediatory proteins (IKK, P-IKB, p65, and P-p65), whereas USP8 overexpression promoted the NF-κB signal by increasing its intermediatory proteins."

reach
"The results show that USP8 can promote the epithelial-to-mesenchymal transition (EMT) process by decreasing E-cadherin and increasing N-cadherin, thereby increasing the PCa cell migration and metastasis."
USP8 affects YY1
| 3
USP8 activates YY1.
| 2
USP8 activates YY1. 2 / 2
| 2

reach
"The effects of USP8 overexpression on SAE mice was reversed secondary to YY1 silencing."

reach
"USP8 overexpression upregulated YY1 and attenuated the brain histopathological damage and cognitive dysfunction in SAE mice."
USP8 increases the amount of YY1.
| 1
USP8 increases the amount of YY1. 1 / 1
| 1

reach
"USP8 upregulated YY1 protein level through deubiquitination, while YY1 was enriched on the USP8 promoter and activated USP8 transcription."
USP8 affects YWHAZ
2 | 1
2 | 1

No evidence text available

reach
"Although the affinity of UBPY for different 14-3-3 isoforms has not been compared, these observations suggest that UBPY exhibits broad binding specificity for 14-3-3 isoforms.A proteomic analysis usin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available
USP8 affects USP8
| 2 1
USP8 increases the amount of USP8.
| 2
USP8 increases the amount of USP8. 2 / 2
| 2

reach
"PTEN deficient cells, which have low levels of USP8 and high levels of FLIP S, were relatively TRAIL resistant, and as previously noted, introduction of WT USP8 (but not blank vector or catalytically inactive USP8) increased USP8 levels and significantly increased the extent of TRAIL induced apoptosis (XREF_FIG)."

reach
"USP8 upregulated YY1 protein level through deubiquitination and YY1 activated USP8 transcription, and USP8-YY1 feedback loop attenuated cognitive dysfunction in SAE mice, which could potentially serve as a novel theoretical foundation for the management of SAE."
USP8 phosphorylates USP8.
| 1
USP8 phosphorylates USP8. 1 / 1
| 1

sparser
"Here, we strengthen these results by showing that deletion of the N-terminal MIT-domain from Usp8 construct 1–504, resulting in Usp8 141–504, almost completely abolished tyrosine phosphorylation ( Fig[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 affects TNFSF10
| 3
Modified USP8 inhibits TNFSF10. 3 / 3
| 3

reach
"Over-expression of WT USP8, but not catalytically inactive USP8, increased FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance, while siRNA mediated suppression of USP8 levels had the opposite effects."

reach
"Overexpression of USP8 increased c-FLIP S ubiquitination, decreased c-FLIP S half-life, decreased c-FLIP S steady-state levels, and decreased TRAIL resistance."

reach
"Overexpression of USP8 increased c-FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance (XREF_FIG)."
USP8 affects SHANK3
1 | 2
USP8 deubiquitinates SHANK3. 3 / 3
1 | 2

reach
"USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity Dependent Protein Levels."

"USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels"

reach
"USP8 acts to deubiquitinate SHANK3, which prevents its proteasomal mediated degradation and enhances overall dendritic spine stability."
USP8 affects SEC31A
1 | 2
USP8 deubiquitinates SEC31A. 3 / 3
1 | 2

reach
"We concluded that USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion."

reach
"Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A."

"Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion"
USP8 affects PTBP1
| 2 1
| 2

reach
"RIP assay also revealed the specific binding of PTBP1 on USP8 in both HEK293T and KCs, which was further boosted when overexpressing MALAT1 in these cells (Fig. 5C)."

reach
"Furthermore, we showed that the binding of PTBP1 to USP8 was significantly promoted by MALAT1."
| 1

sparser
"The impact of METTL3 on m 6 A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays."
USP8 affects OTUB1
1 | 2
1 | 2

sparser
"Otub1 forms a trimolecular complex with USP8 and GRAIL, and upregulated Otub1 promotes GRAIL's proteosomal degradation."

sparser
"USP8 can form a complex with RNF128 and OTUB1 to regulate the anergy of T-cells mediated by RNF128 ( xref )."

No evidence text available
USP8 affects Neoplasms
| 1 2
| 1 2

reach
"Moreover, USP8 depletion attenuated tumor growth upon TRAIL injection in a xenograft model using cervical cancer cells."

reach
"Meanwhile, USP8 deficiency could reduce tumor invasion and migration and tumor size in an immunity-dependent manner, and improve anti-tumor immunogenicity."

eidos
"USP8 promotes cancer progression and extracellular vesicle-mediated CD8 + T cell exhaustion by deubiquitinating the TGF-beta receptor TbetaRII ."
USP8 affects NS1
| 3
| 3

sparser
"One study found that ectopically expressed ZIKV NS1 interacts directly with host de-ubiquitinase USP8 to facilitate the deubiquitination of caspase-1, increasing its stability [ xref ]."

sparser
"(ii) Ubiquitin-mediated negative effect on the host immune response leading to a positive effect on viral replication, e.g., Zika virus (ZIKV) NS1 interacts with USP8 (Ubiquitin Specific Peptidase 8) and causes the deubiquitination of Caspase 1 and prevents its proteasomal degradation."

sparser
"Anti-viral PARP 13 PB2, PA (IAV) ADP ribosylation of the PB2, PA proteins promotes recognition by E3 ubiquitin ligase and subsequent degradation [41] Pro-viral PARP1 Type I Interferon Receptor (IFNAR1) ADP ribosylation by PARP1promotes proteasomal degradation of IFNAR1 during IAV infection [42] (ii) Ubiquitin-mediated negative effect on the host immune response leading to a positive effect on viral replication, e.g., Zika virus (ZIKV) NS1 interacts with USP8 (Ubiquitin Specific Peptidase 8) and causes the deubiquitination of Caspase 1 and prevents its proteasomal degradation."
USP8 affects MET
| 1 1
USP8 decreases the amount of MET.
| 1
USP8 decreases the amount of MET. 1 / 2
| 1

reach
"Ubiquitinated LRIG1 recruits c-Met to lysosomes for degradation; reduction in LRIG1 ubiquitination by USP8 depletion or inactivation thus enables c-Met levels and functionality to be maintained."
USP8 inhibits MET.
| 1
USP8 inhibits MET. 1 / 1
| 1

eidos
"Given that ubiquitin-specific protease 8 ( USP8 ) prevents c-Met degradation by deubiquitination , we performed a preliminary in silico molecular docking and observed that artonin F blocked the catalytic site of USP8 ."
USP8 affects MAP3K7
| 2 1
USP8 binds MAP3K7.
| 1 1
| 1 1

sparser
"Consistently, biochemical results reveal that Usp8 binds Tak1 to remove ubiquitin modification from Tak1, leading to its stabilization."

reach
"Consistently, biochemical results reveal that Usp8 binds Tak1 to remove ubiquitin modification from Tak1, leading to its stabilization."
USP8 deubiquitinates MAP3K7.
| 1
USP8 leads to the deubiquitination of MAP3K7. 1 / 1
| 1

reach
"USP8 promoted the ubiquitination and the degradation of TAK1."
USP8 affects MAGEL2
2 | 1
2 | 1

No evidence text available

No evidence text available

reach
"Specifically, MAGEL2 interacts with TRIM27 and USP7 to modify the ubiquitination and stability of WASH1 [XREF_BIBR], and interacts with RNF41 and USP8 to modify the ubiquitination and stability of the ESCRT-0 (Endosomal Sorting Complexes Required for Transport) complex [XREF_BIBR]."
USP8 affects LDLR
1 | 2
USP8 deubiquitinates LDLR.
1 | 1
USP8 deubiquitinates LDLR. 2 / 2
1 | 1

reach
"We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway."

"We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway."
USP8 ubiquitinates LDLR.
| 1
USP8 ubiquitinates LDLR. 1 / 1
| 1

reach
"Removal of ubiquitin from polyubiquitylated LDLR by USP8 - but not by another ESCRT associated DUB, AMSH (associated molecule with the SH3 domain of STAM) - is a necessary step for receptor entry into[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 affects GRB2
1 2 |
1 2 |

No evidence text available

No evidence text available

No evidence text available
USP8 affects F2RL1
1 | 2
USP8 deubiquitinates F2RL1.
1 | 1
USP8 leads to the deubiquitination of F2RL1. 2 / 2
1 | 1

"Expression of the catalytically inactive mutants, AMSH(D348A) and UBPY(C786S), caused an increase in PAR(2) ubiquitination and trapped the receptor in early endosomes, thereby preventing lysosomal trafficking and degradation."

reach
"USP8 and AMSH mediate deubiquitination of PAR2 and its sorting from endosomes to lysosomes [XREF_BIBR]."
USP8 ubiquitinates F2RL1.
| 1
USP8 ubiquitinates F2RL1. 1 / 1
| 1

reach
"24 USP8 or AMSH knockdown by siRNA results in somewhat greater ubiquitination of PAR2, suggesting that these DUBs regulate PAR2 deubiquitination."
USP8 affects ENaC
| 3
USP8 activates ENaC. 3 / 3
| 3

reach
"USP8 increased ENaC current in Xenopus oocytes and collecting duct epithelia and enhanced ENaC abundance at the cell surface in HEK 293 cells."

reach
"Thus, USP8 and USP2-45 selectively modulate ENaC trafficking at different steps in the endocytic pathway."

reach
"This resulted from altered endocytic sorting; USP8 abolished ENaC degradation in the endocytic pathway, but it had no effect on ENaC endocytosis."
USP8 affects DNAJB6
1 | 1 1
1 | 1 1

reach
"Protein interaction assays showed that sperm UBPy interacts with MSJ-1, the sperm specific DnaJ protein evolutionarily conserved for spermiogenesis."

No evidence text available

sparser
"Protein interaction assays showed that sperm UBPy interacts with MSJ-1, the sperm-specific DnaJ protein evolutionarily conserved for spermiogenesis."
USP8 affects Cyclin
| 3
USP8 increases the amount of Cyclin. 3 / 3
| 3

reach
"The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax."

reach
"The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax."

reach
"The results of western blot showed that knockdown of USP8 down-regulated the expression of cyclin D1, CDK4, and CDK6."
| 3
| 3

reach
"USP8 inhibition markedly reduced cell viability in gefitinib resistant and -sensitive NSCLC cells, but exhibited no observable effects on normal control cells (XREF_FIG)."

reach
"The silencing USP8 and docetaxel treatment reduced cell viability and migration and promoted apoptosis."

reach
"H1975 and H1650 transfected with si-USP8 showed a dramatic decrease in cell viability compared to mock transfected cells, indicating that the suppression of USP8 effectively decreases NSCLC cell viability (XREF_FIG and XREF_SUPPLEMENTARY)."
USP8 affects CTNNB1
| 2 1
USP8 activates CTNNB1. 3 / 3
| 2 1

sparser
"Thus, our study demonstrated that USP8 activated the Wnt/beta-catenin signaling through a post-translational mechanism of β-catenin."

reach
"USP8 and UBPY is reported to activate the Wnt and beta-catenin pathway by targeting Frizzled G protein coupled protein XREF_BIBR."

reach
"Thus, our study demonstrated that USP8 activated the Wnt/beta-catenin signaling through a post-translational mechanism of β-catenin."
USP8 affects CHMP2A
1 | 1 1
1 | 1

reach
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

No evidence text available
| 1

sparser
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
USP8 affects CD274
| 2 1
USP8 inhibits CD274.
| 1
USP8 inhibits CD274. 1 / 1
| 1

reach
"Mechanistically, USP8 inhibition increases PD-L1 protein abundance through elevating the TRAF6-mediated K63-linked ubiquitination of PD-L1 to antagonize K48-linked ubiquitination and degradation of PD-L1."
USP8 increases the amount of CD274.
| 1
USP8 increases the amount of CD274. 1 / 1
| 1

reach
"Mechanically, the binding of lncRNA SNHG12 to HuR improved mRNA stability and expression of PD-L1 and USP8, and USP8-mediated deubiquitination stabilized the protein level of PD-L1."
USP8 binds CD274.
| 1
| 1

sparser
"Moreover, USP8 interacted positively with PD-L1 and upregulated its expression by inhibiting the ubiquitination-regulated proteasome degradation pathway in pancreatic cancer."
USP8 affects BCL2
| 3
USP8 increases the amount of BCL2.
| 2
USP8 increases the amount of BCL2. 2 / 2
| 2

reach
"The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax."

reach
"Jing et al. extended the apoptotic activity of USP8 in cholangiocarcinoma cells, where the silencing of USP8 was reported to decrease Bcl-2 expression and increase Bax, cleaved Caspase 3, and cleaved Caspase 9 expression and thereby triggering apoptosis (18)."
USP8 inhibits BCL2.
| 1
USP8 inhibits BCL2. 1 / 1
| 1

reach
"Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2 and Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells."
USP8 affects BACE1
1 | 2
USP8 decreases the amount of BACE1.
| 2
USP8 decreases the amount of BACE1. 2 / 2
| 2

reach
"Moreover, USP8 depletion increased BACE1 ubiquitination, promoted BACE1 accumulation in the early endosomes and late endosomes and lysosomes, and decreased levels of BACE1 in the recycling endosomes."

reach
"Studies have shown that RNAi mediated depletion of USP8 increased BACE1 ubiquitination on Lys 501, promoted BACE1 accumulation in the early endosomes and late endosomes and lysosomes, and decreased levels of BACE1 in the recycling endosomes."
USP8 deubiquitinates BACE1.
1 |
USP8 deubiquitinates BACE1. 1 / 1
1 |

"The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation"
USP8 affects AURKA
| 1 2
USP8 activates AURKA.
| 1 1
USP8 activates AURKA. 2 / 2
| 1 1

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC

eidos
"CRL3KCTD17 , USP8 , and TCHP TCHP , a centriolar protein originally identified as a keratin-binding protein , activates AURKA and suppresses ciliogenesis [ 101,141,142 ] ."
| PMC
USP8 inhibits AURKA.
| 1
USP8 inhibits AURKA. 1 / 1
| 1

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC
SRC affects USP8
| 1 2
SRC phosphorylates USP8. 3 / 3
| 1 2

reach
"Alternatively, the remaining tyrosine phosphorylation of the Usp8 Delta140 mutant may also indicate that Usp8 is partly phosphorylated by activated Src family kinases in the cytoplasm."

sparser
"Overall, we have provided strong evidence for ligand-induced ERBB- and SRC family kinase-dependent tyrosine phosphorylation of Usp8 1–504."

sparser
"It cannot be excluded that the tyrosine phosphorylation that remains in the ΔMIT mutant may be due to phosphorylation of Usp8 by activated SRC-kinases in the cytoplasm."
SMO affects RACK1
| 3
SMO binds USP8 and RACK1. 3 / 3
| 3

sparser
"In the presence of Hh, Hh dissociates Ci–Rack1 interaction, and promotes Rack1 forming a trimeric complex with Usp8 and Smo, resulting in Smo deubiquitination and cell surface accumulation (Fig.  xref )."

sparser
"The two-step co-IP assay showed that Usp8, Rack1, and Smo formed a trimeric complex (Fig.  xref )."

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
SJB3-019A affects USP8
| 1 2
SJB3-019A inhibits USP8. 3 / 3
| 1 2

reach
"Interestingly, USP2 and USP8, which were both inhibited by SJB3-019A in a previous report, were also inhibited by 42% and 68%, respectively, in our evaluation."
| PMC

reach
"Furthermore, our data indicates that SJB3-019A (XREF_SUPPLEMENTARY), which has previously been shown to inhibit USP1 in leukemic cells 47, inhibits USP8 more strongly (IC 50 0.21 muM) than USP1 (IC 50 1.69 muM) but in addition also significantly inhibited several other DUBs tested."

eidos
"Interestingly , USP2 and USP8 , which were both inhibited by SJB3-019A in a previous report , were also inhibited by 42 % and 68 % , respectively , in our evaluation ."
| PMC
RNF128 affects OTUB1
1 | 2
1 | 2

sparser
"Otub1 forms a trimolecular complex with USP8 and GRAIL, and upregulated Otub1 promotes GRAIL's proteosomal degradation."

sparser
"USP8 can form a complex with RNF128 and OTUB1 to regulate the anergy of T-cells mediated by RNF128 ( xref )."

No evidence text available
RACK1 affects SMO, and USP8
| 3
SMO binds USP8 and RACK1. 3 / 3
| 3

sparser
"In the presence of Hh, Hh dissociates Ci–Rack1 interaction, and promotes Rack1 forming a trimeric complex with Usp8 and Smo, resulting in Smo deubiquitination and cell surface accumulation (Fig.  xref )."

sparser
"The two-step co-IP assay showed that Usp8, Rack1, and Smo formed a trimeric complex (Fig.  xref )."

sparser
"In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation."
PTBP1 affects USP8
| 2 1
| 2

reach
"RIP assay also revealed the specific binding of PTBP1 on USP8 in both HEK293T and KCs, which was further boosted when overexpressing MALAT1 in these cells (Fig. 5C)."

reach
"Furthermore, we showed that the binding of PTBP1 to USP8 was significantly promoted by MALAT1."
| 1

sparser
"The impact of METTL3 on m 6 A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays."
OTUB1 affects RNF128, and USP8
1 | 2
1 | 2

sparser
"Otub1 forms a trimolecular complex with USP8 and GRAIL, and upregulated Otub1 promotes GRAIL's proteosomal degradation."

sparser
"USP8 can form a complex with RNF128 and OTUB1 to regulate the anergy of T-cells mediated by RNF128 ( xref )."

No evidence text available
NS1 affects USP8
| 3
| 3

sparser
"One study found that ectopically expressed ZIKV NS1 interacts directly with host de-ubiquitinase USP8 to facilitate the deubiquitination of caspase-1, increasing its stability [ xref ]."

sparser
"(ii) Ubiquitin-mediated negative effect on the host immune response leading to a positive effect on viral replication, e.g., Zika virus (ZIKV) NS1 interacts with USP8 (Ubiquitin Specific Peptidase 8) and causes the deubiquitination of Caspase 1 and prevents its proteasomal degradation."

sparser
"Anti-viral PARP 13 PB2, PA (IAV) ADP ribosylation of the PB2, PA proteins promotes recognition by E3 ubiquitin ligase and subsequent degradation [41] Pro-viral PARP1 Type I Interferon Receptor (IFNAR1) ADP ribosylation by PARP1promotes proteasomal degradation of IFNAR1 during IAV infection [42] (ii) Ubiquitin-mediated negative effect on the host immune response leading to a positive effect on viral replication, e.g., Zika virus (ZIKV) NS1 interacts with USP8 (Ubiquitin Specific Peptidase 8) and causes the deubiquitination of Caspase 1 and prevents its proteasomal degradation."
MAGEL2 affects USP8
2 | 1
2 | 1

No evidence text available

No evidence text available

reach
"Specifically, MAGEL2 interacts with TRIM27 and USP7 to modify the ubiquitination and stability of WASH1 [XREF_BIBR], and interacts with RNF41 and USP8 to modify the ubiquitination and stability of the ESCRT-0 (Endosomal Sorting Complexes Required for Transport) complex [XREF_BIBR]."
KDR affects USP8
| 2 1
KDR ubiquitinates USP8.
| 1 1
KDR ubiquitinates USP8. 2 / 2
| 1 1

reach
"Based on the above findings, one possibility is that perturbed VEGFR2 endosome-lysosome trafficking is linked to altered VEGFR2 ubiquitination status in USP8 depleted cells."

sparser
"Quantification of immunoblot data showed that whereas ligand‐stimulated VEGFR2 ubiquitination displayed a characteristic peak and decline, under conditions of USP8 depletion VEGFR2 ubiquitination persisted (Figure xref B)."
KDR inhibits USP8.
| 1
KDR inhibits USP8. 1 / 1
| 1

reach
"Quantification of immunoblot data showed that whereas ligand stimulated VEGFR2 ubiquitination displayed a characteristic peak and decline, under conditions of USP8 depletion VEGFR2 ubiquitination persisted."
KCNN4 affects USP8
1 | 1 1
1 | 1

No evidence text available

reach
"Using the DUB Chip, a protein microarray containing 35 DUBs, we demonstrate a time dependent association between KCa3.1 and USP8 following endocytosis, which was confirmed by coimmunoprecipitation."
USP2 binds USP8 and KCNN4. 1 / 1
| 1

sparser
"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."
GRB2 affects USP8
1 2 |
1 2 |

No evidence text available

No evidence text available

No evidence text available
DNAJB6 affects USP8
1 | 1 1
1 | 1 1

reach
"Protein interaction assays showed that sperm UBPy interacts with MSJ-1, the sperm specific DnaJ protein evolutionarily conserved for spermiogenesis."

No evidence text available

sparser
"Protein interaction assays showed that sperm UBPy interacts with MSJ-1, the sperm-specific DnaJ protein evolutionarily conserved for spermiogenesis."
CHMP2A affects USP8
1 | 1 1
1 | 1

reach
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

No evidence text available
| 1

sparser
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
ARL6IP4 affects USP8
| 3
| 3

reach
"USP8 interacts with AIP4 and retains this E3 ubiquitin ligase in a state in which it can interact with FLIP S."

reach
"Collectively, our findings demonstrate a functional cooperation between USP8, AIP4, and the ESCRT-0 machinery at the early sorting phase of CXCR4 and underscore the versatility of USP8 in shaping trafficking events at the early-to-late endosome transition."

reach
"A direct interaction between USP8 and AIP4 has not been reported, and it is possible that instead of directly deubiquitinating AIP4, USP8 may alter the ability of other E3 ligases (or perhaps of AIP4 itself) to stimulate AIP4 K63 polyubiquitination."
Sulforaphane affects USP8
| 2

reach
"In vitro, USP8 binds to SFN and they co-localize at the early endosomes in lung adenocarcinoma cells."

reach
"SFN-USP8 complex deubiquitinates RTKs and facilitates recycling of RTKs to the plasma membrane."
2 |
Sodium arsenate increases the amount of USP8.
1 |
Sodium arsenate increases the amount of USP8. 1 / 1
1 |

No evidence text available
Sodium arsenate decreases the amount of USP8.
1 |
Sodium arsenate decreases the amount of USP8. 1 / 1
1 |

No evidence text available
Snf7 affects USP8
| 2
| 2

sparser
"The MIT-domain of Usp8 interacts with ESCRT-III proteins and is therefore important for endosomal recruitment which is required for EGFR degradation [27,30] ."

sparser
"UBPY binds components of ESCRT-III [ xref ]."
| 2

reach
"The caffeic acid phenethyl ester (CAPE), inhibited ubiquitin-specific protease 8 (USP8), but not proteasomal DUBs in cell-free assays."

reach
"The caffeic acid phenethyl ester (CAPE), inhibited ubiquitin-specific protease 8 (USP8), but not proteasomal DUBs in cell-free assays."
MiR-302a-3p affects USP8
| 1 1
MiR-302a-3p inhibits USP8. 2 / 2
| 1 1

eidos
"We then conducted real time PCR and western blotting to measure the effect of miR-302a-3p on the expression of USP8 , and results indicated that overexpressing miR-302a-3p sharply downregulated USP8 while miR-302a-3p inhibitor significantly increased USP8 ( Figures 5C , D ) ."

reach
"We then conducted real time PCR and western blotting to measure the effect of miR-302a-3p on the expression of USP8, and results indicated that overexpressing miR-302a-3p sharply downregulated USP8 while miR-302a-3p inhibitor significantly increased USP8 (XREF_FIG)."
Iridium atom affects USP8
| 2

sparser
"Other NCIs such as C-H···π between the substrate and the catalyst, C-H···O involving the substrate C-H and the oxygen of the B 2 pin 2 ligand and C-H···N between the substrate and the N atom of the Ir-bound ubpy confirm the significance of such interactions in providing the desirable differential energies between the competing TSs that form the basis of the extent of regioselectivity."

sparser
"Molecular insights into such TSs revealed that the N-H···O interaction between the tethered urea moiety of the Ir-bound ubpy ligand of the catalyst and the amide carbonyl of the substrate is a critical interaction that helps orient the meta C-H bond nearer to iridium."
Indometacin affects USP8
2 |
Indometacin decreases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
2 |
Hsa-miR-95-5p decreases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
2 |
Hsa-miR-4789-3p decreases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
Hsa-miR-466 affects USP8
2 |
Hsa-miR-466 decreases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
Hsa-miR-4643 affects USP8
2 |
Hsa-miR-4643 decreases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
2 |
Hsa-miR-19b-3p decreases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
2 |
Hsa-miR-19a-3p decreases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
Bisphenol A affects USP8
2 |
Bisphenol A increases the amount of USP8. 2 / 2
2 |

No evidence text available

No evidence text available
YWHAG affects USP8
1 1 |
1 1 |

No evidence text available

No evidence text available
USP8 affects ubiquitination TrkB
| 2
USP8 inhibits ubiquitination TrkB. 2 / 2
| 2

eidos
"Immunopurified USP8 deubiquitinates TrkB in vitro whereas knockdown of USP8 results in enhanced ubiquitination of TrkB upon BDNF treatment in neurons ."

eidos
"Immunopurified USP8 deubiquitinates TrkB in vitro whereas knockdown of USP8 results in enhanced ubiquitination of TrkB upon BDNF treatment in neurons ."
USP8 affects sulforaphane
| 2

reach
"In vitro, USP8 binds to SFN and they co-localize at the early endosomes in lung adenocarcinoma cells."

reach
"SFN-USP8 complex deubiquitinates RTKs and facilitates recycling of RTKs to the plasma membrane."
USP8 affects snf7
| 2
| 2

sparser
"The MIT-domain of Usp8 interacts with ESCRT-III proteins and is therefore important for endosomal recruitment which is required for EGFR degradation [27,30] ."

sparser
"UBPY binds components of ESCRT-III [ xref ]."
USP8 affects removal
| 2
USP8 activates removal. 2 / 2
| 2

eidos
"It has been well characterized that ubiquitin-specific protease 8 ( USP8 ) promotes the removal of ubiquitin from SMO , and that HH stimulation promotes the accessibility of the deubiquitinase to SMO [ 51,52 ] ."

eidos
"Effect of USP8 on hOAT1 ubiquitination To examine whether USP8 , a deubiquitination enzyme , specifically catalyzes the removal of ubiquitin from hOAT1 , we transfected hOAT1-expressing cells with USP8 wild type ."
USP8 affects protein
| 2
USP8 activates protein. 2 / 2
| 2

eidos
"Overall , there were 15 proteins that were similarly upregulated by RNAi for UBR4 , STAM , HGS , and USP8 , compared to a control RNAi ."

eidos
"Altogether , RNAi for UBR4 , HGS , STAM , and USP8 led to the upregulation of 672 proteins and to the downregulation of 797 proteins , compared to a control RNAi ( white RNAi ) ."
USP8 affects mitophagy
| 2
| 2

eidos
"USP8 promotes Parkin-mediated mitophagy by deubiquitinating Parkin and promoting its recruitment to the mitochondria ."

eidos
"Usp8 knockdown impairs Parkin-mediated mitophagy by preventing Parkin recruitment of depolarized mitochondria ."
| 2

reach
"USP8 overexpression also reduced the production of lipopolysaccharide (LPS)-induced proinflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2)."

reach
"USP8 overexpression also reduced the production of lipopolysaccharide (LPS)-induced proinflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2)."
USP8 affects iridium atom
| 2

sparser
"Other NCIs such as C-H···π between the substrate and the catalyst, C-H···O involving the substrate C-H and the oxygen of the B 2 pin 2 ligand and C-H···N between the substrate and the N atom of the Ir-bound ubpy confirm the significance of such interactions in providing the desirable differential energies between the competing TSs that form the basis of the extent of regioselectivity."

sparser
"Molecular insights into such TSs revealed that the N-H···O interaction between the tethered urea moiety of the Ir-bound ubpy ligand of the catalyst and the amide carbonyl of the substrate is a critical interaction that helps orient the meta C-H bond nearer to iridium."
USP8 affects ferroptosis
| 1 1
| 1 1

eidos
"High expression of USP8 promoted the progression and inhibited ferroptosis of HCC ."

reach
"High expression of USP8 promoted the progression and inhibited ferroptosis of HCC."
USP8 affects endocytosis
| 2
| 2

reach
"The stimulation of Hh promotes Smo deubiquitination by ubiquitin specific protease 8 (USP8), which blocks Smo endocytosis and enhances Smo cell surface accumulation XREF_BIBR XREF_BIBR."

reach
"AMSH (associated molecule with the SH3 domain of STAM; a JAMM DUB) and USP8/UBPY (ubiquitin-specific protease 8/ubiquitin-specific protease Y) negatively regulate endocytosis by cleaving K63 chains from internalized receptors [53, 54]."
USP8 affects dopamine
| 2
USP8 activates dopamine. 2 / 2
| 2

reach
"USP8 down-regulation completely prevented the loss of PINK1 KO DA neurons (XREF_FIG), restoring dopamine to wild-type levels (XREF_FIG)."

reach
"USP8 KD also prevented Parkin KO DA neurons loss and normalized mitochondrial morphological defects, although it did not ameliorate Parkin climbing performance (XREF_FIG)."
| 1

reach
"USP8 overexpression blocked NGF induced neurites outgrowth while the overexpression of the catalytically inactive mutant USP8 and UBPy (C748A) caused a marked increase of cell differentiation."
| 1

reach
"USP8 overexpression blocked NGF induced neurites outgrowth while the overexpression of the catalytically inactive mutant USP8 and UBPy (C748A) caused a marked increase of cell differentiation."
USP8 affects YWHAG
1 1 |
1 1 |

No evidence text available

No evidence text available
USP8 affects USP25
| 2
| 2

sparser
"For example, this approach has yielded UbVs that bind tightly and selectively to the USP-family DUBs USP8, USP21 or USP2a."

sparser
"Binding selections yielded variants that bound to either USP8, USP21, or USP2a ( xref and xref ) but not to 10 other USPs ( xref )."
USP8 affects UBE2I
2 |
2 |

No evidence text available

No evidence text available
USP8 affects TrkB-dependent neuronal differentiation
| 2
USP8 activates TrkB-dependent neuronal differentiation. 2 / 2
| 2

eidos
"Here , we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 ( USP8 ) modulates BDNF / TrkB-dependent neuronal differentiation ."

eidos
"Here , we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 ( USP8 ) modulates BDNF / TrkB-dependent neuronal differentiation ."
USP8 affects TNF
| 2
USP8 inhibits TNF. 2 / 2
| 2

reach
"USP8 overexpression also attenuated lipopolysaccharide-induced upregulation of TNF-α, IL-6, and IL-1β in BEAS-2B."

reach
"Moreover, USP8 downregulated several pro inflammatory cytokines [nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E 2 (PGE 2), and interleukin-1beta (IL-1beta)] in the serum and brain, and the relevant protein factors [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)] in the brain."
USP8 affects TCHP
| 2
USP8 deubiquitinates TCHP.
| 1
USP8 leads to the deubiquitination of TCHP. 1 / 1
| 1

reach
"Conversely, deubiquitination of TCHP is mediated by ubiquitin-specific peptidase 8 (USP8) [50]."
| PMC
USP8 activates TCHP.
| 1
USP8 activates TCHP. 1 / 1
| 1

reach
"KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50]."
| PMC
USP8 affects SLC22A6
| 2
USP8 increases the amount of SLC22A6. 2 / 2
| 2

reach
"In addition, COS-7 cells have fair amount of endogenous USP8, which perhaps have already increased hOAT1 expression and activity to certain extent."

reach
"The protein levels of cell membrane protein marker E-cadherin (XREF_FIG, bottom panel) and cell total protein marker beta-actin (XREF_FIG, bottom panel) were not affected under these conditions, thereby indicating that the change in hOAT1 expression induced by USP8 wild type transfection was not due to the general perturbation of membrane and cellular proteins."
USP8 affects SFN
1 | 1
1 | 1

No evidence text available

reach
"Kim et al report that USP8 can specifically bind to stratifin (SFN) protein in lung adenocarcinoma cells, and knockdown of USP8 or SFN gene leads to down-regulation of tumor cell proliferation and up-regulation of apoptosis."
USP8 affects SCNN1B
2 |
2 |

No evidence text available

No evidence text available
USP8 affects SAIT301
| 2
USP8 inhibits SAIT301. 2 / 2
| 2

reach
"Over-expression of USP8 significantly reversed SAIT301 mediated degradation of both LRIG1 and Met while USP8-CS had no such impact (XREF_FIG)."

reach
"Over-expression of USP8 almost completely reversed SAIT301 induced growth inhibition of EBC1 cells."
USP8 affects RASGRF1
1 |
1 |

No evidence text available

reach
"Notable examples include: the UCH family member BRCA1-associated protein 1 (BAP1), mutated in melanoma, mesothelioma and renal cell carcinoma ; USP6, translocated in aneurysmal bone cysts ; USP7, mutated in neurological disorders ; USP8, whose mutations cause Cushing disease ; USP9X, whose mutations cause developmental disorders and whose expression is dysregulated in cancer ; USP15, amplified in certain glioblastoma, breast and ovarian cancers ; and CYLD, commonly mutated in cylindromatosis ."
USP8 affects PTEN
2 |
2 |

No evidence text available

No evidence text available
USP8 affects POMC promoter
| 2
USP8 activates POMC promoter. 2 / 2
| 2

reach
"Ectopic expression of USP8 mutants or cleaved USP8 in murine corticotroph cell line induced higher POMC promoter activity and transcription than wild-type USP8."

reach
"In the absence of EGFR, USP8 was unable to augment the POMC promoter activity in luciferase reporter assay, and gefitinib, an EGFR inhibitor, significantly impaired the ACTH production in primary corticotroph adenoma cells [XREF_BIBR, XREF_BIBR]."
USP8 affects PINK1
| 2
USP8 activates PINK1. 2 / 2
| 2

reach
"USP8 down-regulation rescues mitochondria defects of PINK1 KO flies."

reach
"USP8 down-regulation completely prevented the loss of PINK1 KO DA neurons (XREF_FIG), restoring dopamine to wild-type levels (XREF_FIG)."
USP8 affects NBR1
2 |
2 |

No evidence text available

No evidence text available
USP8 affects LEPR
| 2
USP8 deubiquitinates LEPR. 2 / 2
| 2

reach
"USP8 deubiquitinates the leptin receptor and is necessary for leptin mediated synapse formation."

reach
"Bland and colleagues suggested that leptin increases the expression of USP8, which in turn deubiquitylates the leptin receptor by cleaving Lys48-ubiquitin chains, among other (still unknown) chain types."
USP8 affects KIF23
1 1 |
1 1 |

No evidence text available

No evidence text available
USP8 affects JNK
| 2
USP8 activates JNK. 2 / 2
| 2

reach
"Usp8 promotes tumor cell migration through activating the JNK pathway."

reach
"In addition, human USP8 also triggers tumor cell migration and activates the JNK pathway."
USP8 affects IL7R
| 2
USP8 activates IL7R. 2 / 2
| 2

reach
"Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [XREF_BIBR]."

reach
"Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [81]."
USP8 affects IL1B
| 2
USP8 inhibits IL1B. 2 / 2
| 2

reach
"USP8 overexpression also attenuated lipopolysaccharide-induced upregulation of TNF-α, IL-6, and IL-1β in BEAS-2B."

reach
"Moreover, USP8 downregulated several pro inflammatory cytokines [nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E 2 (PGE 2), and interleukin-1beta (IL-1beta)] in the serum and brain, and the relevant protein factors [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)] in the brain."
USP8 affects ID1
| 2
USP8 inhibits ID1.
| 1
USP8 inhibits ID1. 1 / 1
| 1

reach
"Ectopic expression of USP8 promotes ESCC tumorigenesis by suppressing ID1 degradation, whereas knockdown of USP8 results in the opposite phenotypes in vitro and in vivo."
USP8 increases the amount of ID1.
| 1
USP8 increases the amount of ID1. 1 / 1
| 1

reach
"USP8 interacts with ID1, and increases the protein level and stability of ID1 by reducing its ubiquitination."
USP8 affects HAT1
| 1 1
USP8 inhibits HAT1. 2 / 2
| 1 1

eidos
"Interestingly , HAT1 is upregulated also by USP8 loss but it is not regulated by RNAi for HGS , STAM ."

reach
"Interestingly, HAT1 is upregulated also by USP8 loss but it is not regulated by RNAi for HGS, STAM."
USP8 affects GST
| 1 1
| 1 1

reach
"GST-Gads, but not GST alone, bound to UBPY, Gab2, and BLNK."

sparser
"Pull-down assays showed that bacterially purified GST-USP8 bound trichoplein in RPE1 lysates (Fig.  xref )."
USP8 affects ESCRT-III subunits
| 2
USP8 binds ESCRT-III subunits. 2 / 2
| 2

reach
"For example, specific ESCRT-III subunits bind more tightly to the VPS4 ATPases, the VPS4 activator Vta1p and LIP5, the adaptor protein ALIX (CHMP4A-C), and the ubiquitin hydrolases AMSH (CHMP1A and 3) and UBPY (CHMP1A, 1B, 2A, 4C, and 7)."

reach
"For example, specific ESCRT-III subunits bind more tightly to the VPS4 ATPases (Stuchell-Brereton et al., 2007), the VPS4 activator Vta1p and LIP5 (Azmi et al., 2008; Shim et al., 2008; Xiao et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 affects ESCRT
| 2
USP8 binds ESCRT. 2 / 2
| 2

reach
"AMSH and USP8 and ESCRT complexes."

reach
"Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB."
USP8 affects EPAS1
| 2
USP8 binds EPAS1 and HIF1A. 2 / 2
| 2

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [75]."

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [ xref ]."
USP8 affects EGF
| 2
USP8 activates EGF. 2 / 2
| 2

reach
"Cleavage of USP8 led to increased deubiqutination of the EGF receptor, impairing its downregulation and sustaining EGF signaling."

reach
"XREF_BIBR Cleavage of USP8 led to increased deubiquitination of the epidermal growth factor receptor (EGFR), impairing its downregulation and sustaining EGF signaling."
USP8 affects Death
| 2
USP8 activates Death. 2 / 2
| 2

reach
"Silencing or pharmacological inhibition of USP8 deubiquitinase, relevant in particular to the stability of RTKs such as EGFR and MET, was shown to induce death of gefitinib resistant NSCLC cells in vitro and in vivo [XREF_BIBR]."

reach
"USP8 siRNAs reduced viability and increased death in cSCC lines but had little effect in normal skin cells (XREF_FIG a)."

reach
"Indeed, inhibition of USP8 either by its knockdown or synthetic small molecule led to attenuation of variety of receptor tyrosine kinase (RTK) activities, resulting in the inhibition of cell proliferation in gefitinib-resistant and -sensitive non-small cell lung cancer (NSCLC) cells [47] ."
USP8 affects CYT1
| 2
USP8 deubiquitinates CYT1. 2 / 2
| 2

reach
"Finally, CYT-1 is not subjected to deubiquitination by the K63 polyubiquitin specific AMSH DUB enzyme, while CYT-1 is slightly deubiquitinated by USP8."

reach
"Finally, even though CYT-1 shows ligand induced K63 polyubiquitination, it is not subjected to deubiquitination by the K63 polyubiquitin specific AMSH deubiquitinating enzyme, while CYT-1 is slightly deubiquitinated by USP8."
USP8 affects CHMP4C
2 |
2 |

No evidence text available

No evidence text available
USP8 affects CHMP proteins
| 2
USP8 binds CHMP proteins. 2 / 2
| 2

reach
"AMSH and USP8 can also interact with CHMP proteins that are components of the late ESCRT-III machinery XREF_BIBR, XREF_BIBR."

reach
"In common with other MIT containing proteins such as AMSH and VPS4, UBPY can interact with CHMP proteins, which are known to regulate endosomal sorting of ubiquitinated receptors."
USP8 affects CCR7
| 1 1
USP8 inhibits CCR7. 2 / 2
| 1 1

reach
"Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [81]."

eidos
"Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [ 81 ] ."
USP8 affects Ala-Gly-Ser
| 2
| 2

reach
"Therefore, we found that down-regulation of USP8 could significantly inhibit the cell-cycle of AGS and block the G1 phase."

reach
"Therefore, it was confirmed that down-regulation of USP8 could inhibit the proliferation of NCI-N87, MKN-45 and AGS cell lines, which is HER-3 positive GC cells."
USP8 affects AVPR1B
| 2
Mutated USP8 activates AVPR1B. 2 / 2
| 2

reach
"Comparably, Avpr1b promoter activity was enhanced by the overexpression of mutant USP8 compared to the wild type."

reach
"The present data suggest that USP8 mutations upregulate the AVPR1B promoter activity."
USP8 affects AKT1
| 2
USP8 increases the amount of AKT1. 2 / 2
| 2

reach
"Although the decreased PI3K and P-Akt levels were found by silenced EGFR, the overexpressed USP8 was shown to increase PI3K/P-Akt expression over EGFR silencing and thereby increase the NF-kB signal activation ( Figure 7 )."

reach
"Thereby, together with these data, it can be concluded that the elevated level of USP8 not only increases the expression of EGFR, PI3K, and P-Akt but also might increase the PI3K and P-Akt expression over EGFR silencing where the PI3K and P-Akt well established the downstream target of EGFR ( Figures 6C, D )."
USP8 affects AIP4
| 2
USP8 binds AIP4. 2 / 2
| 2

sparser
"A direct interaction between USP8 and AIP4 has not been reported, and it is possible that instead of directly deubiquitinating AIP4, USP8 may alter the ability of other E3 ligases (or perhaps of AIP4 itself) to stimulate AIP4 K63 polyubiquitination ( xref )."

sparser
"USP8 interacts with AIP4 and retains this E3 ubiquitin ligase in a state in which it can interact with FLIP S . Under these conditions FLIP S undergoes ubiquitin-mediated degradation, leaving the cell susceptible to TRAIL-induced apoptosis."
USP25 affects USP8
| 2
| 2

sparser
"For example, this approach has yielded UbVs that bind tightly and selectively to the USP-family DUBs USP8, USP21 or USP2a."

sparser
"Binding selections yielded variants that bound to either USP8, USP21, or USP2a ( xref and xref ) but not to 10 other USPs ( xref )."
UBE2I affects USP8
2 |
2 |

No evidence text available

No evidence text available
TMEM79 affects FZD
| 2
FZD binds USP8 and TMEM79. 2 / 2
| 2

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"These data together suggest that the assembly of the FZD-USP8-TMEM79 complex, in which USP8 action on FZD is inhibited specifically, probably is multivalent in nature and involves additional proteins yet to be identified."
SMO affects HGS
| 2
SMO binds USP8 and HGS. 2 / 2
| 2

sparser
"However, we found that Hrs blocks Smo phosphorylation ( xref ), whereas USP8 does not xref , suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"It is possible that Hrs competes with USP8 for binding Smo, as Hrs and USP8 directly interact with the same domain of Smo."
SFN affects USP8
1 | 1
1 | 1

No evidence text available

reach
"Kim et al report that USP8 can specifically bind to stratifin (SFN) protein in lung adenocarcinoma cells, and knockdown of USP8 or SFN gene leads to down-regulation of tumor cell proliferation and up-regulation of apoptosis."
SCNN1B affects USP8
2 |
2 |

No evidence text available

No evidence text available
SAIT301 affects USP8
| 2
SAIT301 inhibits USP8. 2 / 2
| 2

reach
"This result suggests that SAIT301 perturbs USP8 mediated modulation of LRIG1, resulting in the degradation of LRIG1."

reach
"These results support the hypothesis that the presence of USP8 may affect the potency of anti-tumor efficacy of SAIT301, and SAIT301 may benefit from concomitant inhibition of USP8 for improved efficacy."
RNAi affects USP8
| 2
RNAi inhibits USP8. 2 / 2
| 2

reach
"We sought to understand the mechanism by which Hh reduces Smo ubiquitination and found that the inactivation of USP8 by RNAi or by the expression of a dominant negative USP8 abolished the effects of Hh on Smo ubiquitination."

reach
"We also found that inactivation of USP8 by RNAi or by USP8C> S overexpression caused an enlargement of the early endosome (XREF_FIG and XREF_FIG), which was consistent with a previous finding that USP8 deficient mouse primary cells exhibit enlarged early endosomes XREF_BIBR."
RASGRF1 affects USP8
1 |
1 |

No evidence text available
RA-9 affects USP8
| 2
RA-9 inhibits USP8. 2 / 2
| 2

reach
"RA-9, a chalcone derivative with a structure similar to b-AP15, was reported to inhibit proteasomal DUBs [XREF_BIBR] as well as UCHL1, UCHL3, USP2, USP5, and USP8 [XREF_BIBR]."

reach
"Indeed, it was found that RA-9 inhibited in vitro UCHL1, UCHL3, USP8 and USP9x, besides USP14 and UCHL5."
PTEN affects USP8
2 |
2 |

No evidence text available

No evidence text available
NTRK2 affects USP8
| 2
| 2

sparser
"USP8 binds to the C-terminus of TrkB using its microtubule interacting domain (MIT)."

sparser
"USP8 binds to the C-terminus of TrkB using its microtubule interacting domain (MIT)."
NBR1 affects USP8
2 |
2 |

No evidence text available

No evidence text available
MAP3K7 affects USP8
| 1 1
| 1 1

sparser
"Consistently, biochemical results reveal that Usp8 binds Tak1 to remove ubiquitin modification from Tak1, leading to its stabilization."

reach
"Consistently, biochemical results reveal that Usp8 binds Tak1 to remove ubiquitin modification from Tak1, leading to its stabilization."
KIF23 affects USP8
1 1 |
1 1 |

No evidence text available

No evidence text available
HIF1A affects EPAS1
| 2
USP8 binds EPAS1 and HIF1A. 2 / 2
| 2

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [75]."

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [ xref ]."
HGS affects SMO, and USP8
| 2
SMO binds USP8 and HGS. 2 / 2
| 2

sparser
"However, we found that Hrs blocks Smo phosphorylation ( xref ), whereas USP8 does not xref , suggesting that Hrs and USP8 bind Smo in different conformation."

sparser
"It is possible that Hrs competes with USP8 for binding Smo, as Hrs and USP8 directly interact with the same domain of Smo."
GST affects USP8
| 1 1
| 1 1

reach
"GST-Gads, but not GST alone, bound to UBPY, Gab2, and BLNK."

sparser
"Pull-down assays showed that bacterially purified GST-USP8 bound trichoplein in RPE1 lysates (Fig.  xref )."
FZD affects TMEM79, and USP8
| 2
FZD binds USP8 and TMEM79. 2 / 2
| 2

sparser
"Mechanistically, TMEM79 forms a complex with FZD and USP8 and inhibits USP8 deubiquitination of FZD during biogenesis, thereby promoting trafficking of ubiquitinated FZD from ER to the lysosome for destruction ( xref )."

sparser
"These data together suggest that the assembly of the FZD-USP8-TMEM79 complex, in which USP8 action on FZD is inhibited specifically, probably is multivalent in nature and involves additional proteins yet to be identified."
ESCRT-III subunits affects USP8
| 2
USP8 binds ESCRT-III subunits. 2 / 2
| 2

reach
"For example, specific ESCRT-III subunits bind more tightly to the VPS4 ATPases, the VPS4 activator Vta1p and LIP5, the adaptor protein ALIX (CHMP4A-C), and the ubiquitin hydrolases AMSH (CHMP1A and 3) and UBPY (CHMP1A, 1B, 2A, 4C, and 7)."

reach
"For example, specific ESCRT-III subunits bind more tightly to the VPS4 ATPases (Stuchell-Brereton et al., 2007), the VPS4 activator Vta1p and LIP5 (Azmi et al., 2008; Shim et al., 2008; Xiao et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
ESCRT affects USP8
| 2
USP8 binds ESCRT. 2 / 2
| 2

reach
"AMSH and USP8 and ESCRT complexes."

reach
"Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB."
EPS15 affects USP8
2 |
2 |

No evidence text available

No evidence text available
EPAS1 affects USP8
| 2
USP8 binds EPAS1 and HIF1A. 2 / 2
| 2

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [75]."

sparser
"USP8 binds to the PERN-ARNT-SIM (PAS) domain of HIF-1α and HIF-2α and protect them from VHL-mediated ubiquitination [ xref ]."
CUL3 affects USP8
| 1 1
CUL3 ubiquitinates USP8. 2 / 2
| 1 1

reach
"However, the protein levels of USP8 and AMSH seem unchanged upon Cul3-depletion, implying that Cul3 ubiquitination of USP8 and AMSH does not trigger their degradation."

sparser
"However, the protein levels of USP8 and AMSH seem unchanged upon Cul3-depletion, implying that Cul3 ubiquitination of USP8 and AMSH does not trigger their degradation."
CLOCK affects USP8
| 1 1
| 1 1

sparser
"As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK/CYC transcriptional activity."

reach
"As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK and CYC transcriptional activity."
CHMP4C affects USP8
2 |
2 |

No evidence text available

No evidence text available
CHMP proteins affects USP8
| 2
USP8 binds CHMP proteins. 2 / 2
| 2

reach
"AMSH and USP8 can also interact with CHMP proteins that are components of the late ESCRT-III machinery XREF_BIBR, XREF_BIBR."

reach
"In common with other MIT containing proteins such as AMSH and VPS4, UBPY can interact with CHMP proteins, which are known to regulate endosomal sorting of ubiquitinated receptors."
AIP4 affects USP8
| 2
USP8 binds AIP4. 2 / 2
| 2

sparser
"A direct interaction between USP8 and AIP4 has not been reported, and it is possible that instead of directly deubiquitinating AIP4, USP8 may alter the ability of other E3 ligases (or perhaps of AIP4 itself) to stimulate AIP4 K63 polyubiquitination ( xref )."

sparser
"USP8 interacts with AIP4 and retains this E3 ubiquitin ligase in a state in which it can interact with FLIP S . Under these conditions FLIP S undergoes ubiquitin-mediated degradation, leaving the cell susceptible to TRAIL-induced apoptosis."
1 |
Titanium dioxide increases the amount of USP8. 1 / 1
1 |

No evidence text available
SiRNA2 affects USP8
| 1
SiRNA2 decreases the amount of USP8. 1 / 1
| 1

reach
"As shown in Figure 1A and B, the transfection of siRNA1 and siRNA2 significantly reduced the mRNA and protein expression of USP8 in the cells (P<0.05)."
SiRNA USP8 affects USP8
| 1
SiRNA USP8 inhibits USP8. 1 / 1
| 1

eidos
"SiRNA USP8 ( A ) depleted USP8 to the greatest extent , and this was associated with reduced expression of growth factor receptors MET , EGFR , and ERBB2 , along with HGS and STAM2 ."
PCMV3-USP8 affects USP8
| 1
PCMV3-USP8 activates USP8. 1 / 1
| 1

eidos
"PCMV3-USP8 significantly increased USP8 expression , whereas no changes in the USP8 expression by knockdown of EGFR were found ."
Nocodazole affects USP8
| 1
| 1

reach
"HeLa cells transfected with FLAG-UBPY were treated with or without nocodazole, and FLAG-UBPY was immunopurified from their lysates in the same way as in Fig. 3."
Luteolin affects USP8
| 1
| 1

reach
"Taken together, our findings suggested that luteolin inhibits microglial inflammation by enhancing USP8 protein production."
Jinfukang affects USP8
1 |
Jinfukang decreases the amount of USP8. 1 / 1
1 |

No evidence text available
Ionomycin affects USP8
1 |
Ionomycin decreases the amount of USP8. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4753-5p decreases the amount of USP8. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-132-3p decreases the amount of USP8. 1 / 1
1 |

No evidence text available
Doxorubicin affects USP8
1 |
Doxorubicin decreases the amount of USP8. 1 / 1
1 |

No evidence text available
1 |
Dexamethasone decreases the amount of USP8. 1 / 1
1 |

No evidence text available
Artonin F affects USP8
| 1
Artonin F inhibits USP8. 1 / 1
| 1

reach
"Given that ubiquitin-specific protease 8 (USP8) prevents c-Met degradation by deubiquitination, we performed a preliminary in silico molecular docking and observed that artonin F blocked the catalytic site of USP8."
[1,2-b]pyrazine-2,3-dicarbonitrile affects USP8
| 1
[1,2-b]pyrazine-2,3-dicarbonitrile activates USP8. 1 / 1
| 1

reach
"9-Ethyloxyimino-9H-indeno [1,2-b] pyrazine-2,3-dicarbonitrile, a recently synthesized inhibitor of USP8 (XREF_FIG), effectively attenuated the deubiquitinating activity of USP8 in vitro (XREF_FIG)."
WP1130 affects USP8
| 1
WP1130 inhibits USP8. 1 / 1
| 1

eidos
"For example , 8-mercapto-N - ( ( tetrahydro-3-furanyl ) methyl ) -4 - quinoline carboxamide , LND-57444 , VLX1570 , ML323 , ( ADC-01 , ADC-03 , HBX41108 , HBX19818 , P5091 , P22077 ) , 9 - ( ethoxyimino ) -9 H-indeno ( 1,2 - b ) pyrazine-2 ,3 - dicarbonitrile , WP1130 , Mitoxantrone and GSK2643943A are able to inhibit PSMD14 , UCHL1 , UCHL5 and USP14 , USP1 , USP7 , USP8 , USP9X , USP11 and USP20 , respectively ."
1 |

No evidence text available
VPS4B affects USP8
1 |
1 |

No evidence text available
Ubiquitin affects RNF41
| 1
| 1

sparser
"There was evidence that Magel2 was involved in the leptin-POMC of the hypothalamus to maintain the energy balance of the body.[ xref ]Wijesuriya et al have found that MAGEL2 and Necdin connected leptin receptor (LepR) to the USP8-RNF41 ubiquitin complex through the LepR adapter protein, IRS4."
| 1

sparser
"We demonstrate that the pivotal β-cell mitophagy regulator, CLEC16A, is an E3 ligase that forms a ubiquitin-dependent tripartite complex with RNF41/NRDP1 and USP8."
USP8 affects α-syn
| 1
USP8 increases the amount of α-syn. 1 / 1
| 1

reach
"Importantly, the knockdown of USP8 significantly reduces α-syn levels in SH-SY5Y human cells."

reach
"It is very likely that USP8 mutation activates the transcription of POMC via multiple pathways including the NF-κB pathway."
USP8 affects proteolysis
| 1
| 1

reach
"Further studies indicated that AUF1 protein degradation was mediated by upregulating USP8 transcription, which was modulated by its negative regulatory transcription factor Sp1."
USP8 affects protein stability ID1
| 1
USP8 activates protein stability ID1. 1 / 1
| 1

eidos
"USP8 interacts with ID1 , and increases the protein level and stability of ID1 by reducing its ubiquitination ."

reach
"In conclusion, USP8 inhibited lipopolysaccharide-triggered inflammation and pyroptosis in human bronchial epithelial cells by activating PI3K/AKT signaling and inhibiting NF-κB signaling pathway."
USP8 affects procollagen IV
| 1
USP8 inhibits procollagen IV. 1 / 1
| 1

reach
"By contrast, USP8 knockdown caused the accumulation of COPII coat proteins around the cis-Golgi, promoted the intracellular trafficking of procollagen IV from the endoplasmic reticulum to the Golgi, and increased collagen IV secretion."
USP8 affects poly-ubiquitin chains
| 1
USP8 activates poly-ubiquitin chains. 1 / 1
| 1

reach
"Stefan et al. discovered and structurally identified the first covalent inhibitor of NEDD4-1, which switches the mechanism of NEDD4-1 from processive to distributive, following which NEDD4-1 synthesizes the attachment of poly-ubiquitin chains to the substrate in the presence of the deubiquitinating enzyme USP8 ."
USP8 affects pathway
| 1
USP8 activates pathway. 1 / 1
| 1

sparser
"In addition, human USP8 also triggers tumor cell migration and activates the JNK pathway."
USP8 affects osteogenic differentiation
| 1
USP8 activates osteogenic differentiation. 1 / 1
| 1

eidos
"USP8 promotes osteogenic differentiation by blocking the ubiquitination of Wnt receptor frizzled 5 ( FZD5 ) to stabilize the Wnt / beta-catenin signaling pathway ( Chaugule et al ., 2021 ) ."
USP8 affects neuregulin receptor
| 1
USP8 activates neuregulin receptor. 1 / 1
| 1

reach
"Researchers have found that USP8 markedly enhanced the stability of neuregulin receptor degradation protein-1 (Nrdp1), which in turn inhibited the production of proinflammatory cytokines in toll like receptor triggered macrophages."
USP8 affects morphology
| 1
USP8 activates morphology. 1 / 1
| 1

eidos
"While the enzymes mediating SHANK ubiquitination are not known , it has been recently found that USP8 selectively deubiquitinates SHANK1 and SHANK3 and modulates dendritic spine density and morphology ( Campbell and Sheng , 2018 ) ."
USP8 affects migration
| 1
USP8 activates migration. 1 / 1
| 1

eidos
"In contrast , USP8 knockdown suppressed melanoma cell growth , survival and migration , and augmented the inhibitory effects of therapeutic drugs ."
USP8 affects melanoma cell growth
| 1
USP8 activates melanoma cell growth. 1 / 1
| 1

eidos
"In contrast , USP8 knockdown suppressed melanoma cell growth , survival and migration , and augmented the inhibitory effects of therapeutic drugs ."
USP8 affects linked chains
| 1
USP8 leads to the deubiquitination of linked chains on K63. 1 / 1
| 1

reach
"In particular, accumulation of K63-linkedubiquitin in LB disease was found to be partly caused by an increase in the levels of the Usp8, an enzyme that deubiquitinates K63 linked chains on alpha-synuclein leading to a decrease of its degradation via the lysosomal pathway [XREF_BIBR]."
USP8 affects inhibitory therapeutic drugs
| 1
USP8 inhibits inhibitory therapeutic drugs. 1 / 1
| 1

eidos
"In contrast , USP8 knockdown suppressed melanoma cell growth , survival and migration , and augmented the inhibitory effects of therapeutic drugs ."
USP8 affects inhibitive miR-302a-3p ossification
| 1
USP8 activates inhibitive miR-302a-3p ossification. 1 / 1
| 1

eidos
"These findings suggest that USP8 mediates the inhibitive effect of miR-302a-3p on ossification ."
USP8 affects hormonogenesis ..
| 1
USP8 activates hormonogenesis ... 1 / 1
| 1

eidos
"Present findings support that USP8 gene expression levels may contribute to pitutary tumorigenesis and hormonogenesis .."
| 1

reach
"Interestingly, we found only K252R mutant EPG5, but not WT or △LC3 mutant EPG5, could compensate the defective colony formation and pluripotent gene expression lead by USP8 deterioration (Supplementary Figure 7c–e)."
USP8 affects gastric cancer cell
| 1
USP8 activates gastric cancer cell. 1 / 1
| 1

eidos
"USP8 regulates NF-kappaB activation through EGFR and PI3K stabilization to promote PCa cell proliferation and survival In multiple studies ( 29-32 ) , the EGFR is a substrate of USP8 deubiquitination , while USP8 has been shown to enhance gastric cancer cell proliferation and metastasis via the PI3K / AKT signaling pathway ( 30 ) ."
USP8 affects gain-of-function USP8 protein
| 1
USP8 activates gain-of-function USP8 protein. 1 / 1
| 1

eidos
"Mutations in the ubiquitin specific peptidase 8 ( USP8 ) gene , which causes gain-of-function of USP8 protein , are highly prevalent in Cushing disease ( 133 ) ."

trips
"USP8 suppresses death receptor-mediated apoptosis by enhancing FLIPL stability."
USP8 affects extracellular vesicle-mediated CD8
| 1
USP8 activates extracellular vesicle-mediated CD8. 1 / 1
| 1

eidos
"USP8 promotes cancer progression and extracellular vesicle-mediated CD8 + T cell exhaustion by deubiquitinating the TGF-beta receptor TbetaRII ."
| 1
USP8 decreases the amount of ethylenediamine. 1 / 1
| 1

reach
"Moreover, inactivation of USP8 by either USP8RNAi or USP8C> S in Drosophila embryo down-regulated En expression (XREF_FIG, compare to wild-type En staining in H) and caused lethality of the embryo or pupa (unpublished data)."
USP8 affects dpp-lacZ
| 1
Modified USP8 increases the amount of dpp-lacZ. 1 / 1
| 1

reach
"Co-expression of Flag-USP8 with GFP-Smo by MS1096 Gal4 caused induction of dpp-lacZ and ptc expression in A-compartment cells both close to and away from the A/P boundary (XREF_FIG), whereas the expression of Flag-USP8 alone did not induce ectopic dpp-lacZ and ptc expression (XREF_FIG)."
USP8 affects dominant negative mutant protein
| 1
USP8 activates dominant negative mutant protein. 1 / 1
| 1

reach
"USP8 downregulation or overexpression of a dominant negative mutant protein results in enhanced ubiquitination and transcriptional activity of CLK [XREF_BIBR] (XREF_FIG)."
USP8 affects distinct protein targets
| 1
USP8 activates distinct protein targets. 1 / 1
| 1

eidos
"However , we find that HGS , STAM , USP8 , and UBR4 also modulate distinct protein targets ."
USP8 affects circulating extracellular vesicles
| 1
USP8 activates circulating extracellular vesicles. 1 / 1
| 1

eidos
"USP8 expression also enables TbetaRII + circulating extracellular vesicles ( crEVs ) to induce T cell exhaustion and chemoimmunotherapy resistance ."
USP8 affects chains
| 1
USP8 inhibits chains. 1 / 1
| 1

reach
"AMSH (associated molecule with the SH3 domain of STAM; a JAMM DUB) and USP8/UBPY (ubiquitin-specific protease 8/ubiquitin-specific protease Y) negatively regulate endocytosis by cleaving K63 chains from internalized receptors [53, 54]."
| 1

reach
"USP8 knockdown markedly induced apoptosis and cell cycle arrest ( G 0/ G 1)."
USP8 affects assess synergism proteasome
| 1
USP8 activates assess synergism proteasome. 1 / 1
| 1

eidos
"Depleting USP5 or USP8 to assess the synergism with proteasome inhibitor ( Bortezomib ) were measured ."
USP8 affects alpha-syn SH-SY5Y human cells
| 1
USP8 activates alpha-syn SH-SY5Y human cells. 1 / 1
| 1

eidos
"Importantly , the knockdown of USP8 significantly reduces alpha-syn levels in SH-SY5Y human cells ."
USP8 affects activity
| 1
USP8 inhibits activity. 1 / 1
| 1

sparser
"However, it is as yet unknown whether USP8 is mutated in AtT20 cells and whether the increased deubiquitination activity of mutated USP8 can be inhibited by a USP8 inhibitor."
USP8 affects activation NF-kappaB pro-inflammatory cytokines
| 1
USP8 inhibits activation NF-kappaB pro-inflammatory cytokines. 1 / 1
| 1

eidos
"Zhang et al. found that USP8 suppresses the IHR-induced activation of NF-kappaB and pro-inflammatory cytokines production by removing K63-linked polyubiquitination moieties from TAK1 ( 118 ) ."
USP8 affects accumulation Cx43
| 1
USP8 inhibits accumulation Cx43. 1 / 1
| 1

eidos
"Thus , we propose that , in the absence of AMSH , ubiquitinated Cx43 is mainly directed to degradation , while lack of USP8 results in the accumulation of Cx43 , likely at late endosomes / MVBs , modified with ubiquitin chains that favor its sorting into ILVs that will be subsequently secreted as EVs ( Bejarano et al , 2012 ; Martins-Marques et al , 2015c ) ."
USP8 affects abundance cell surface receptors
| 1
USP8 activates abundance cell surface receptors. 1 / 1
| 1

eidos
"We also utilized UbVs to reduce the abundance and activity of cell surface receptors by inhibiting USP8 , an enzyme that regulates levels of epidermal growth factor receptor ( EGFR ) and other receptors ( Fig. 5b ) ( Ernst et al ., 2013 ) ."
USP8 affects abnormalities caused mutant HTT
| 1
USP8 activates abnormalities caused mutant HTT. 1 / 1
| 1

eidos
"However , loss of USP8 does not prevent abnormalities caused by mutant HTT ( Alexopoulou et al. 2016 ) ."
USP8 affects Wnt receptor
| 1
Modified USP8 increases the amount of Wnt receptor. 1 / 1
| 1

reach
"Loss of USP8 leads to hyperubiquitination and enhanced degradation of EGF, MET, and ERBB3 receptors XREF_BIBR, XREF_BIBR but increases the level of the Wnt receptor Frizzled by enhancing receptor recycling 59."
USP8 affects VPS4B
1 |
1 |

No evidence text available
USP8 affects USP8 inhibitor
| 1
USP8 inhibits USP8 inhibitor. 1 / 1
| 1

reach
"The relation of Met, LRIG1 and USP8 strongly supports the potential clinical benefit of a combination treatment of a USP8 inhibitor and a Met inhibitor, such as SAIT301."
USP8 affects USP46
| 1
USP8 deubiquitinates USP46. 1 / 1
| 1

reach
"In addition to USP46, USP8 can also deubiquitinate mammalian AMPARs indicating that multiple regulatory mechanisms exist to control AMPAR ubiquitination levels (Scudder et al., 2014)."
USP8 affects USP2
| 1
USP2 binds USP8 and KCNN4. 1 / 1
| 1

sparser
"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."
USP8 affects UBE2E1
1 |
1 |

No evidence text available
USP8 affects TSEN2
1 |
1 |

No evidence text available
USP8 affects TRIM63
1 |
1 |

No evidence text available
USP8 affects TRIM54
1 |
1 |

No evidence text available
USP8 affects TP53
| 1
USP8 decreases the amount of TP53. 1 / 1
| 1

reach
"Importantly, knockdown of USP8 inhibited activation of the Akt signaling pathway by decreasing the phosphorylation level of Akt and up-regulated p53 expression, while USP8 overexpression increased activation of the Akt signaling pathway in Hucct-1 cells."
USP8 affects TGFBR2
| 1
USP8 activates TGFBR2. 1 / 1
| 1

eidos
"USP8 expression also enables TbetaRII + circulating extracellular vesicles ( crEVs ) to induce T cell exhaustion and chemoimmunotherapy resistance ."
USP8 affects TGF-beta SMAD-induced epithelial-mesenchymal transition EMT invasion metastasis tumor cells
| 1
USP8 activates TGF-beta SMAD-induced epithelial-mesenchymal transition EMT invasion metastasis tumor cells. 1 / 1
| 1

eidos
"USP8 promotes TGF-beta / SMAD-induced epithelial-mesenchymal transition ( EMT ) , invasion , and metastasis in tumor cells ."
USP8 affects SSTR5
| 1
USP8 increases the amount of SSTR5. 1 / 1
| 1

reach
"As mutated USP8 also increases SSTR5 expression, CAs with USP8 mutation respond better to treatment with the somatostatin analogue pasireotide which acts through SSTR5."
USP8 affects SH3 domain
| 1
STAM binds USP8 and SH3 domain. 1 / 1
| 1

reach
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner."
USP8 affects SCNN1G
1 |
1 |

No evidence text available
USP8 affects RTK
| 1
USP8 leads to the ubiquitination of RTK. 1 / 1
| 1

reach
"One set of studies indicates that Usp8 and UBPY mediated de-ubiquitination reduces the lysosomal degradation of RTKs such as EGFR [XREF_BIBR]."
USP8 affects RP23-78H4.1
1 |
USP8 binds RP23-78H4.1. 1 / 1
1 |

No evidence text available
USP8 affects RIPK2
| 1
USP8 activates RIPK2. 1 / 1
| 1

reach
"USP8 promoted RIPK2-mediated NF-κB activation."
USP8 affects PDCD6IP
| 1
| 1

sparser
"Nonetheless, HBP/STAM, ALIX, and UBPY binding gave robust signals in WT ubiquitin binding assays, and binding was abolished when the ubiquitin hydrophobic patch was mutated (I44A), ( xref )."
USP8 affects OPRM1
| 1
| 1

reach
"Although the interaction between Mop, Cbl, Ubpy, and Hrs seems to play a role in the recycling of Fz, our present findings do not exclude a role for other unidentified proteins in this molecular cascade."
USP8 affects Maintenance
| 1
| 1

eidos
"Consequently , we conclude that Clec16a , Nrdp1 , and USP8 assemble in a tripartite ubiquitin-dependent mitophagy complex to promote maintenance of Parkin ."
USP8 affects MAPK
| 1
Mutated USP8 activates MAPK. 1 / 1
| 1

reach
"Previous studies have demonstrated that the USP8 mutation causes corticotroph adenomas mainly through activating the EGFR–MAPK signal cascades ."
USP8 affects MAP1LC3
| 1
USP8 inhibits MAP1LC3. 1 / 1
| 1

reach
"Importantly, USP8 knock down did not impair LC3 conversion upon mTOR inhibition (XREF_SUPPLEMENTARY), further indicating that our observed effects on NCOA4 and ferritin protein levels do not reflect a general block in autophagic capacity."
USP8 affects MALAT1
| 1
| 1

sparser
"The impact of METTL3 on m 6 A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays."
USP8 affects LYN
| 1
USP8 binds DAPP1 and LYN. 1 / 1
| 1

sparser
"For example, SOS1 and SOS2 strongly associated with the signalosomes at 5-min time point, whereas USP8, LYN, and DAPP1 interacted more strongly after 15 min of BCR stimulation (Fig xref , Supplementary Table xref )."
USP8 affects KRT36
1 |
1 |

No evidence text available
USP8 affects K63-Ub-BRIT1
| 1
USP8 leads to the deubiquitination of K63-Ub-BRIT1. 1 / 1
| 1

reach
"Our recent study has revealed such a cellular process that deubiquitination of K63-Ub-BRIT1 at the region of aa 566-655 mediated by the Dub USP8 is needed for targeting BRIT1 to site of damaged chromatin [XREF_BIBR]."
USP8 affects K6-linked Parkin ubiquitination
| 1
USP8 inhibits K6-linked Parkin ubiquitination. 1 / 1
| 1

eidos
"Utilizing a mutant ubiquitin only capable of K6-linked conjugates , we observed the expected reduction of K6-linked Parkin ubiquitination by USP8 ( Fig. 4F ) ."
USP8 affects K6 ubiquitination
| 1
USP8 activates K6 ubiquitination. 1 / 1
| 1

eidos
"While Parkin auto-inhibition and K6 ubiquitination are relieved by USP8 to promote its mitochondrial localization , it is unclear how Clec16a opposes USP8-mediated deubiquitination of Parkin ."
USP8 affects IL6
| 1
USP8 inhibits IL6. 1 / 1
| 1

reach
"USP8 overexpression also attenuated lipopolysaccharide-induced upregulation of TNF-α, IL-6, and IL-1β in BEAS-2B."
USP8 affects ID1-TXNIP
| 1
USP8 activates ID1-TXNIP. 1 / 1
| 1

reach
"Moreover, we found that TXNIP is a novel downstream target of ID1, and USP8 promotes ESCC tumorigenesis by activating the ID1-TXNIP pathway."
USP8 affects HRS
| 1
STAM binds USP8, STAMBP, and HRS. 1 / 1
| 1

sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
USP8 affects HNRNPD
| 1
USP8 inhibits HNRNPD. 1 / 1
| 1

reach
"Further studies indicated that AUF1 protein degradation was mediated by upregulating USP8 transcription, which was modulated by its negative regulatory transcription factor Sp1."
USP8 affects GST14-3-3
| 1
USP8-Y679F binds GST14-3-3. 1 / 1
| 1

reach
"Our experiment showed that Usp8 Y679F binds to GST14-3-3 with the same affinity as Usp8 WT and Usp8 C748, while binding of Usp8 S680A to 14-3-3 was largely abolished."
USP8 affects GAB2
| 1
USP8 binds BLNK, GAB2, and GRAP2. 1 / 1
| 1

sparser
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."
USP8 affects Fzd receptors
| 1
USP8 deubiquitinates Fzd receptors. 1 / 1
| 1

reach
"In contrast, Fzd receptors are deubiquitinated by UBPY and ubiquitin specific protease 6 and 8 (USP6 and USP8)."
USP8 affects FZD8
1 |
USP8 deubiquitinates FZD8 on lysine. 1 / 1
1 |

No evidence text available
USP8 affects FARSB
1 |
1 |

No evidence text available
USP8 affects ESR1
| 1
| 1

sparser
"Overall, our findings suggest that DC-U4106 is a promising drug candidate and targeting the USP8-ERα complex could be a new approach to treat ER-positive or drug-resistant breast cancer."
USP8 affects ESCRT-III complex
| 1
USP8 binds ESCRT-III complex. 1 / 1
| 1

reach
"Once internalized cargo has been committed for degradation, conjugated ubiquitin must be recycled and removed by endosomal DUBs such as USP8, which also associate with the ESCRT and III complex on late endosomes 8, 18."
USP8 affects ESCRT-0
| 1
USP8 activates ESCRT-0. 1 / 1
| 1

reach
"71 In contrast to PAR2, USP8 (or AMSH) does not impact CXCR4 ubiquitination but instead modulates the ubiquitin status of ESCRT-0 that is ubiquitinated by the E3 ligase AIP4, 23 reinforcing the idea that ubiquitination of the transport machinery represents an important regulatory event in GPCR trafficking."
USP8 affects EEA1
| 1
USP8 activates EEA1. 1 / 1
| 1

reach
"VEGFR2 also accumulated in EEA1 positive early endosomes when cells were treated with individual USP8 siRNAs to limit off-target effects."
USP8 affects DAPP1
| 1
USP8 binds DAPP1 and LYN. 1 / 1
| 1

sparser
"For example, SOS1 and SOS2 strongly associated with the signalosomes at 5-min time point, whereas USP8, LYN, and DAPP1 interacted more strongly after 15 min of BCR stimulation (Fig xref , Supplementary Table xref )."
| 1

reach
"Moreover, mutations in the Usp8 and Usp48 loci in pituitary tumors cause Cushing syndrome."
USP8 affects Collagen
| 1
| 1

reach
"By contrast, USP8 knockdown caused the accumulation of COPII coat proteins around the cis-Golgi, promoted the intracellular trafficking of procollagen IV from the endoplasmic reticulum to the Golgi, and increased collagen IV secretion."
USP8 affects CHMP3
| 1
| 1

sparser
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
USP8 affects CHMP2B
1 |
1 |

No evidence text available
USP8 affects CDK6
| 1
USP8 increases the amount of CDK6. 1 / 1
| 1

reach
"The results of western blot showed that knockdown of USP8 down-regulated the expression of cyclin D1, CDK4, and CDK6."
USP8 affects CD63
| 1
USP8 activates CD63. 1 / 1
| 1

reach
"In addition, the enlarged VEGFR2 positive endosomes did not co-distribute with late endosome marker, CD63, in cells treated with individual USP8 siRNAs."
USP8 affects CBL
| 1
USP8 deubiquitinates CBL-Y1091F. 1 / 1
| 1

reach
"Indeed, the Y1045F and Y1091F Cbl binding site mutants are deubiquitinated by Usp8, suggesting that this ubiquitination signal may represent mono- or oligo-ubiquitin (Figs. 7 and 8, upper panel, arrow[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP8 affects CASP3
| 1
USP8 activates CASP3. 1 / 1
| 1

reach
"In contrast, the elevated expression of USP8 greatly reduced the proportion of apoptotic PCa cells ( Figure 5B ) and reduced the cleaved Caspase 3 and cleaved Caspase 9 which were found in DU145 and PC3 cells by USP8 overexpression ( Figures 6A, B )."
USP8 affects BLNK
| 1
USP8 binds BLNK, GAB2, and GRAP2. 1 / 1
| 1

sparser
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."
USP8 affects BECN1
| 1
USP8 leads to the deubiquitination of BECN1. 1 / 1
| 1

reach
"USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction."
USP8 affects BAX
| 1
USP8 decreases the amount of BAX. 1 / 1
| 1

reach
"The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax."
USP8 affects AVP
| 1
USP8 binds STAMBP and AVP. 1 / 1
| 1

sparser
"Like Doa4 in yeast, mammalian Usp8 and AMSH associate with class E Vps proteins on endosomes."
USP8 affects ATF4
| 1
USP8 binds ATF4-S245A. 1 / 1
| 1

reach
"In agreement with our hypothesis, the ATF4 S245A mutant bound to less USP8 than WT ATF4 (XREF_FIG)."
USP8 affects APP
| 1
USP8 inhibits APP. 1 / 1
| 1

reach
"The endosome related deubiquitinating enzyme ubiquitin specific peptidase 8 (USP8) may inhibit the degradation of MVBs by regulating APP intracellular domain (AICD) protein levels [XREF_BIBR]."
| PMC
USP8 affects AP1
| 1
Mutated USP8 activates AP1. 1 / 1
| 1

reach
"The murine Sstr5 promoter has two binding sites for the activating protein 1 (AP-1) and USP8 mutants possibly mediate their action by stimulating AP-1 transcriptional activity."
USP2 affects USP8
| 1
USP2 binds USP8 and KCNN4. 1 / 1
| 1

sparser
"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."
USP1 inhibitors affects USP8
| 1
USP1 inhibitors activates USP8. 1 / 1
| 1

reach
"Furthermore, we could show that SJB3-019A and Pimozide, two proposed USP1 inhibitors XREF_BIBR, XREF_BIBR, inhibit USP8 at a ten-fold lower concentration or showed poorly selectivity, respectively."
UBE2E1 affects USP8
1 |
1 |

No evidence text available
TSEN2 affects USP8
1 |
1 |

No evidence text available
TRIM63 affects USP8
1 |
1 |

No evidence text available
TRIM54 affects USP8
1 |
1 |

No evidence text available
TGFA affects USP8
| 1
TGFA leads to the dephosphorylation of USP8 on tyrosine. 1 / 1
| 1

reach
"This model is supported by our current findings that TGFalpha stimulation of EGFR and EGF stimulation of ERBB2 [52], conditions that are associated with enhanced endosomal recycling and decreased MVB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Src-family kinases affects USP8
| 1
Src-family kinases phosphorylates USP8. 1 / 1
| 1

reach
"Alternatively, the remaining tyrosine phosphorylation of the Usp8 Delta140 mutant may also indicate that Usp8 is partly phosphorylated by activated Src family kinases in the cytoplasm."
STAMBP affects HRS
| 1
STAM binds USP8, STAMBP, and HRS. 1 / 1
| 1

sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
STAMBP affects HGS
| 1
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
STAMBP affects CHMP3
| 1
| 1

sparser
"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
STAMBP affects AVP
| 1
USP8 binds STAMBP and AVP. 1 / 1
| 1

sparser
"Like Doa4 in yeast, mammalian Usp8 and AMSH associate with class E Vps proteins on endosomes."
STAM affects SH3 domain
| 1
STAM binds USP8 and SH3 domain. 1 / 1
| 1

reach
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner."
STAM affects HRS
| 1
STAM binds USP8, STAMBP, and HRS. 1 / 1
| 1

sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
STAM affects HGS
| 1
STAM binds USP8, STAMBP, and HGS. 1 / 1
| 1

sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
SP1 affects USP8
| 1
SP1 increases the amount of USP8. 1 / 1
| 1

reach
"Some studies demonstrated that specific protein 1 (Sp1) decreased USP8 transcription."
SH3 domain affects USP8
| 1
STAM binds USP8 and SH3 domain. 1 / 1
| 1

reach
"The molecular mechanism underlying these opposing effects is hinted at by the observation that USP8 and AMSH bind a central SH3 domain of STAM proteins in a mutually exclusive manner."
SCNN1G affects USP8
1 |
1 |

No evidence text available
RTK affects USP8
| 1
RTK phosphorylates USP8. 1 / 1
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sparser
"Western blotting confirmed that knockdown of USP8 not only reduced RTK phosphorylation, but also the total levels of EGFR, ERBB2, ERBB3, and MET in H1975 and H1650 cells ( xref )."
RP23-78H4.1 affects USP8
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USP8 binds RP23-78H4.1. 1 / 1
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No evidence text available
RORA affects USP8
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RORA decreases the amount of USP8. 1 / 1
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No evidence text available
RNF43 affects USP8
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RNF43 ubiquitinates USP8. 1 / 1
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"The cell-surface receptor Fz is ubiquitinated by the transmembrane E3 ligases ZNRF3 and RNF43 and is deubiquitinated by UBPY/Ub-specific protease 8 (USP8) for recycling to the plasma membrane (69, 70)."
RNF41 affects Ubiquitin
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sparser
"There was evidence that Magel2 was involved in the leptin-POMC of the hypothalamus to maintain the energy balance of the body.[ xref ]Wijesuriya et al have found that MAGEL2 and Necdin connected leptin receptor (LepR) to the USP8-RNF41 ubiquitin complex through the LepR adapter protein, IRS4."
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sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."
RNF41 affects BIRC6
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USP8 binds BIRC6 and RNF41. 1 / 1
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sparser
"USP8 interactions with Nrdp1 and BRUCE."
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Particulate Matter decreases the amount of USP8. 1 / 1
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No evidence text available
PTBP1 affects MALAT1
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sparser
"The impact of METTL3 on m 6 A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays."
PSMD14 affects USP8
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PSMD14 activates USP8. 1 / 1
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"Therefore, a second process involving DUBs is the recycling of ubiquitin by preventing its degradation, which is mediated by proteasome associated DUBs USP14, UCH-L5 and UCH37, and POH1, or receptor mediated endocytosis and lysosomal degradation associated DUBs USP8 and AMSH."
PDGFR affects USP8
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PDGFR activates USP8. 1 / 1
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sparser
"In RPE1 cells, EGFR knockdown is sufficient to repress the USP8-trichoplein-Aurora A axis and induce ciliogenesis, however, we do not exclude the involvement of other RTKs in other cell types since USP8 is also activated by PDGFRs and FGFR1-mediated phosphorylation in vitro (Supplementary Fig.  xref )."
PDCD6IP affects USP8
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sparser
"Nonetheless, HBP/STAM, ALIX, and UBPY binding gave robust signals in WT ubiquitin binding assays, and binding was abolished when the ubiquitin hydrophobic patch was mutated (I44A), ( xref )."
OPRM1 affects USP8
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"Although the interaction between Mop, Cbl, Ubpy, and Hrs seems to play a role in the recycling of Fz, our present findings do not exclude a role for other unidentified proteins in this molecular cascade."
NMDAR affects USP8
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NMDAR activates USP8. 1 / 1
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"Upon AMPAR stimulation, Nedd4-1 is rapidly redistributed to dendritic spines while NMDAR stimulation selectively activates USP8."
Mice affects USP8
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Mice increases the amount of USP8. 1 / 1
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"Melatonin, however, upregulated USP8 expression, thus maintaining the stability of NICD and Notch signaling, which ultimately reduced EC injury in our sepsis model and elevated the survival rate of septic mice."
ML364 affects USP8
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ML364 inhibits USP8. 1 / 1
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"Of note, ML364 also inhibits USP8 to a degree similar to USP2 due to the similarity between the active sites of the two enzymes 31."
MET affects USP8
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MET inhibits USP8. 1 / 1
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sparser
"Consistently, USP8 inhibition by USP8i decreased p-EGFR (~90%), EGFR (~70%), p-c-Met (~50%) and c-Met (~60%) in HCC cells respectively ( xref , xref )."
MALAT1 affects USP8
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sparser
"The impact of METTL3 on m 6 A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays."
LYN affects USP8
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USP8 binds DAPP1 and LYN. 1 / 1
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sparser
"For example, SOS1 and SOS2 strongly associated with the signalosomes at 5-min time point, whereas USP8, LYN, and DAPP1 interacted more strongly after 15 min of BCR stimulation (Fig xref , Supplementary Table xref )."
LEP affects USP8
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LEP increases the amount of USP8. 1 / 1
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"Bland and colleagues suggested that leptin increases the expression of USP8, which in turn deubiquitylates the leptin receptor by cleaving Lys48-ubiquitin chains, among other (still unknown) chain types."
KRT36 affects USP8
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No evidence text available
KCNN4 affects USP2, and USP8
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USP2 binds USP8 and KCNN4. 1 / 1
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sparser
"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."
ITCH affects CFLAR
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USP8 binds ITCH and CFLAR. 1 / 1
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sparser
"USP8-regulated ITCH binding to c-FLIP mediates c-FLIP ubiquitination in cancer cells incubated with 9F7-F11."
IL2R affects USP8
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IL2R leads to the deubiquitination of ubiquitinated USP8. 1 / 1
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"In particular, IL-2R signaling leads to Akt and mTOR activation, Otub1 translation, de-ubiquitination of ubiquitinated USP8, and subsequent degradation of GRAIL that permits T cell proliferation."
IGF1 affects USP8
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IGF1 inhibits USP8. 1 / 1
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"Further, IGF-1 could reverse the inhibitory effects of USP8 knockdown on the Akt signaling pathway and the proliferation of QBC939 and RBE cells."
HRS affects USP8
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STAM binds USP8, STAMBP, and HRS. 1 / 1
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sparser
"Ubiquitylation is a highly dynamic process, and Ub is ultimately removed from cargoes prior to MVB vesicle incorporation by the deubiquitylating ESCRT enzymes, UBPY or AMSH, which interact with both the HRS:STAM adaptor and ESCRT-III subunits ( xref , xref )."
HGS affects STAMBP
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STAM binds USP8, STAMBP, and HGS. 1 / 1
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sparser
"UBPY and AMSH interact with the Hrs-STAM complex and counteract ubiquitination of RTKs."
HER-3 affects USP8
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HER-3 increases the amount of USP8. 1 / 1
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isi
"Patients with high expression of USP8 or HER-3 tumors alone died earlier than those with low expression and the patients with both USP8 and HER-3 high expression had a shorter overall survival than those with the opposite pattern (both USP8 and HER-3 low expression)."
GW 7647 affects USP8
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GW 7647 inhibits USP8. 1 / 1
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"Moreover, GW7647 did not inhibit USP5 and USP8."
GST14-3-3 affects USP8
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USP8-Y679F binds GST14-3-3. 1 / 1
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"Our experiment showed that Usp8 Y679F binds to GST14-3-3 with the same affinity as Usp8 WT and Usp8 C748, while binding of Usp8 S680A to 14-3-3 was largely abolished."
GSK2643943A affects USP8
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GSK2643943A inhibits USP8. 1 / 1
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eidos
"For example , 8-mercapto-N - ( ( tetrahydro-3-furanyl ) methyl ) -4 - quinoline carboxamide , LND-57444 , VLX1570 , ML323 , ( ADC-01 , ADC-03 , HBX41108 , HBX19818 , P5091 , P22077 ) , 9 - ( ethoxyimino ) -9 H-indeno ( 1,2 - b ) pyrazine-2 ,3 - dicarbonitrile , WP1130 , Mitoxantrone and GSK2643943A are able to inhibit PSMD14 , UCHL1 , UCHL5 and USP14 , USP1 , USP7 , USP8 , USP9X , USP11 and USP20 , respectively ."
GRAP2 affects GAB2
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USP8 binds BLNK, GAB2, and GRAP2. 1 / 1
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sparser
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."
FLVCR1 affects USP8
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FLVCR1 activates USP8. 1 / 1
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"Similar results were also found in docetaxel treatment where PI3K, phosphorylated IκBα, and p65 were significantly lower than USP8-overexpressing PCa cells."
FGFR affects USP8
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FGFR leads to the phosphorylation of USP8. 1 / 1
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"Together, the results indicate that the blockade of the FGF/FGFR system by extracellular or intracellular inhibitors exerts a significant impact on the primary cilium in TRAMP-C2 cells.Activation of different tyrosine kinase receptors suppresses ciliogenesis in retinal epithelial cells by stabilizing the trichoplein-Aurora A complex following phosphorylation of the deubiquitinase USP8 [39]."
FARSB affects USP8
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No evidence text available
ESR1 affects USP8
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sparser
"Overall, our findings suggest that DC-U4106 is a promising drug candidate and targeting the USP8-ERα complex could be a new approach to treat ER-positive or drug-resistant breast cancer."
ESCRT-III affects USP8
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USP8 binds ESCRT-III. 1 / 1
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reach
"In this scenario, UBPY, bound to ESCRT-III, should have sufficient reach to deubiquitinate EGFR and thus destabilise the structure, triggering ILV involution as a prelude to membrane scission."
ESCRT-III complex affects USP8
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USP8 binds ESCRT-III complex. 1 / 1
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"Once internalized cargo has been committed for degradation, conjugated ubiquitin must be recycled and removed by endosomal DUBs such as USP8, which also associate with the ESCRT and III complex on late endosomes 8, 18."
ERBB3 affects USP8
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sparser
"In addition, antibody treatment disrupted the basal USP8-HER3 interaction to favor ITCH-mediated HER3 ubiquitination and proteasomal degradation."
EGFR-ErbB2 chimera affects USP8
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EGFR-ErbB2 chimera activates USP8. 1 / 1
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"In the context of a chimeric EGFR-ErbB2 receptor, we have shown that (i) EGF induced K63 linked polyubiquitination of the ErbB2 cytoplasmic tail occurs efficiently in a pY1091 dependent manner, (ii) c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
EGFR-ERBB4 CYT-1 affects USP8
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EGFR-ERBB4 CYT-1 leads to the phosphorylation of USP8 on tyrosine. 1 / 1
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reach
"These results show that EGF stimulation of EGFR-ERBB4 CYT-1 triggers USP8 tyrosine phosphorylation and demonstrate that USP8 is part of the ERBB4 signaling cascade."

sparser
"We determined a significant interaction between OTUB1 and USP8, RNF128, LRIG1, UBB, UBC, STAM2, RNF41, EGFR, RPS27A, and HGS by PPI."
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sparser
"We demonstrate that the pivotal β-cell mitophagy regulator, CLEC16A, is an E3 ligase that forms a ubiquitin-dependent tripartite complex with RNF41/NRDP1 and USP8."
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sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."
E3-DUB affects USP8
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E3-DUB ubiquitinates USP8. 1 / 1
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"These data suggest a reciprocal E3-DUB relationship in which GRAIL can ubiquitinate USP8, and ubiquitinated USP8 can de-ubiquitinate GRAIL."
DUB-specifi c affects USP8
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DUB-specifi c activates USP8. 1 / 1
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eidos
"HBX 90,397 , another DUB-specifi c inhibitor , blocks USP8 activity ."
| PMC
DAPP1 affects USP8
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USP8 binds DAPP1 and LYN. 1 / 1
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sparser
"For example, SOS1 and SOS2 strongly associated with the signalosomes at 5-min time point, whereas USP8, LYN, and DAPP1 interacted more strongly after 15 min of BCR stimulation (Fig xref , Supplementary Table xref )."
CLEC16A affects E3_Ub_ligase, RNF41, and USP8
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sparser
"We have recently shown that upstream regulation of mitophagy in beta cells relies on formation of a protein complex comprising the E3 ligases CLEC16A and NRDP1 and the deubiquitinase USP8 1 ."
CHMP3 affects USP8
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"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
CHMP2B affects USP8
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No evidence text available
CHMP2A affects STAMBP
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"CHMP1 (Did2), CHMP2 (Vps2) and CHMP3 (Vps24) can interact with two mammalian deubiquitinating enzymes, AMSH and UBPY, to facilitate their recruitment directly [ xref , xref , xref ]."
CFLAR affects ITCH, and USP8
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USP8 binds ITCH and CFLAR. 1 / 1
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sparser
"USP8-regulated ITCH binding to c-FLIP mediates c-FLIP ubiquitination in cancer cells incubated with 9F7-F11."
CD274 affects USP8
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sparser
"Moreover, USP8 interacted positively with PD-L1 and upregulated its expression by inhibiting the ubiquitination-regulated proteasome degradation pathway in pancreatic cancer."
BLNK affects USP8
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USP8 binds BLNK, GAB2, and GRAP2. 1 / 1
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sparser
"The novel interactions between Gads and UBPY, BLNK, and Gab2 were confirmed by in vitro binding experiments using GST-Gads fusion proteins."
BIRC6 affects RNF41, and USP8
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USP8 binds BIRC6 and RNF41. 1 / 1
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sparser
"USP8 interactions with Nrdp1 and BRUCE."
Aroclor 1254 affects USP8
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Aroclor 1254 decreases the amount of USP8. 1 / 1
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No evidence text available
AVP affects USP8
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USP8 binds STAMBP and AVP. 1 / 1
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sparser
"Like Doa4 in yeast, mammalian Usp8 and AMSH associate with class E Vps proteins on endosomes."
ATF4 affects USP8
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USP8 binds ATF4-S245A. 1 / 1
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"In agreement with our hypothesis, the ATF4 S245A mutant bound to less USP8 than WT ATF4 (XREF_FIG)."
AKT1 affects USP8
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AKT1 phosphorylated on Y474, T308, and S473 phosphorylates USP8 on threonine. 1 / 1
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No evidence text available
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No evidence text available