IndraLab
Statements
USP8 is modified
27
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176
36
USP8 is phosphorylated.
27
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141
36
rlimsp
"We further show that Usp8 tyrosine phosphorylation upon stimulation of EGFR-ErbB2 is (a) independent of Y1091, (b) dependent on Src- and EGFR-ErbB2-kinase activity, (c) enhanced upon coexpression of Usp8-C748A, and (d) partly dependent on the Microtubule Interacting and Transport (MIT) domain of Usp8."
USP8 is phosphorylated. 9 / 9
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9
sparser
"In hepatocellular carcinoma, the STE20-like kinase (SLK) mediates the phosphorylation of the S716 site of USP8, significantly enhancing its binding ability to OGT; interestingly, the catalytic subunit alpha of protein phosphatase 1 (PPP1CA) can reverse this binding effect through dephosphorylation [ xref ]."
USP8 is phosphorylated on tyrosine. 5 / 5
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5
USP8 is phosphorylated on Y810. 5 / 5
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5
USP8 is phosphorylated on Y717. 2 / 2
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2
rlimsp
"As described earlier, USP8 knockdown induced trichoplein degradation and unscheduled ciliogenesis, whereas these phenomena were ameliorated by expression of endogenous level of FLAG-USP8 WT (Fig. 7e, f; 10 ng ml−1 of Dox). In contrast, equal levels of Y717F/Y810F had only a modest effect, suggesting that phosphorylations of Tyr-717 and Tyr-810 are important for trichoplein-mediated inhibition of ciliogenesis."
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."
USP8 is ubiquitinated.
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27
USP8 is dephosphorylated.
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8
USP8 deubiquitinates EGFR phosphorylated on Y1016, K754, K737, Y1197, K970, K929, K867, Y1172, Y1110, Y1092, and Y1069 on K716. 3 / 3
3
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USP8 deubiquitinates EGFR phosphorylated on Y1016, K754, K737, K716, Y1197, K970, K929, Y1172, Y1110, Y1092, and Y1069 on K867. 3 / 3
3
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USP8 deubiquitinates EGFR phosphorylated on Y1016, K754, K737, K716, Y1197, K929, K867, Y1172, Y1110, Y1092, and Y1069 on K970. 3 / 3
3
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USP8 deubiquitinates EGFR phosphorylated on Y1016, K754, K716, Y1197, K970, K929, K867, Y1172, Y1110, Y1092, and Y1069 on K737. 3 / 3
3
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USP8 deubiquitinates EGFR phosphorylated on Y1016, K737, K716, Y1197, K970, K929, K867, Y1172, Y1110, Y1092, and Y1069 on K754. 3 / 3
3
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USP8 deubiquitinates EGFR phosphorylated on Y1016, K754, K737, K716, Y1197, K970, K867, Y1172, Y1110, Y1092, and Y1069 on K929. 3 / 3
3
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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
"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)."
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
"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
"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
)."
sparser
"Several lines of evidence suggest that the ubiquitin pathway regulates Smo endocytic trafficking and degradation: (1) Smo was accumulated in mutant clones lacking the ubiquitin-activating enzyme Uba1 in wing imaginal discs, and inactivation of Uba1 in S2 cells inhibited Smo ubiquitination and promoted its cell surface accumulation; (2) Smo was accumulated when the activity of several endocytic components or lysosome was inhibited; (3) Hh and PKA/CK1-mediated Smo phosphorylation inhibited Smo ubiquitination and increased Smo cell surface expression; (4) the Smo autoinhibitory domain (SAID) promoted receptor ubiquitination and internalization; (5) Smo was ubiquitinated at multiple sites both inside and outside the SAID domain and mutating the ubiquitin acceptor sites in SAID increased Smo half-life and cell surface expression; and (6) Smo cell surface expression was promoted by the deubiquitinating enzyme UBPY that binds Smo and counteracts Smo ubiquitination."
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."
reach
"The catalytic domain of USP8 (USP8NT3) was sufficient to reduce Smo ubiquitination (XREF_FIG, lane 4, top panel), enhance the accumulation of endogenous Smo (XREF_FIG), and increase the GFP-Smo-mediated induction of ectopic dpp-lacZ and ptc expression (XREF_FIG, XREF_SUPPLEMENTARY '' ')."
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
"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."
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 clarify whether impaired ubiquitination affected the Clec16a-Nrdp1-USP8 complex as a result of reduced levels of constituents or by impaired complex assembly, we also doubled the amount of Flag-Clec16a plasmid in the presence of KO ubiquitin, resulting in increased levels of Clec16a, USP8, and Nrdp1 (Fig. 4E, lane ++)."
reach
"Collectively, these findings suggest that functional ubiquitination is necessary for maintaining levels of the constituents of the Clec16a-Nrdp1-USP8 complex as well as providing vital signals for complex assembly.USP8 shares functional overlap with Clec16a/Nrdp1 in the regulation of mitophagic flux, coinciding in their opposing regulation of the E3 ligase Parkin, a critical effector in mitophagy (34)."
reach
"These results suggest, again, that Clec16a drives assembly of the Clec16a-Nrdp1-USP8 complex by providing essential ubiquitin signals and stabilizing its component proteins.To determine whether the Clec16a-Nrdp1-USP8 axis regulates β-cell function, we assessed the role of Clec16a-mediated ubiquitination on GSIS in Min6 β-cells."
reach
"SNAIL1, a key regulator of dedifferentiation, is stabilized in esophageal squamous cell carcinoma, breast cancer cells, and lung carcinoma cells by set of DUBs including OTUB1, DUB3, and USP37, respectively.36 37 38 DUB3 has also been shown to deubiquitinate SLUG and TWIST, the other two essential regulators of dedifferentiation.39 Recent few reports provided information on direct impact of DUBs on β-cell physiology.40 CLEC16A-RNF41 and USP8 form a tripartite complex, wherein CLEC16A is an E3 ligase that ubiquitinates RNF41 and USP8 is the DUB that deubiquitinates RNF41."
reach
"Furthermore, in a previous study, USP8 increased NRDP1 levels, potently downregulated MyD88 and TLR4 levels, and blocked inhibitor of NF-κB kinase subunit β and IκBα phosphorylation, thus decreasing p65 nuclear translocation, resulting in and inhibition of NF-κB signaling pathway activation in LPS-induced mice (12)."
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."
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 clarify whether impaired ubiquitination affected the Clec16a-Nrdp1-USP8 complex as a result of reduced levels of constituents or by impaired complex assembly, we also doubled the amount of Flag-Clec16a plasmid in the presence of KO ubiquitin, resulting in increased levels of Clec16a, USP8, and Nrdp1 (Fig. 4E, lane ++)."
reach
"Collectively, these findings suggest that functional ubiquitination is necessary for maintaining levels of the constituents of the Clec16a-Nrdp1-USP8 complex as well as providing vital signals for complex assembly.USP8 shares functional overlap with Clec16a/Nrdp1 in the regulation of mitophagic flux, coinciding in their opposing regulation of the E3 ligase Parkin, a critical effector in mitophagy (34)."
reach
"These results suggest, again, that Clec16a drives assembly of the Clec16a-Nrdp1-USP8 complex by providing essential ubiquitin signals and stabilizing its component proteins.To determine whether the Clec16a-Nrdp1-USP8 axis regulates β-cell function, we assessed the role of Clec16a-mediated ubiquitination on GSIS in Min6 β-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]."
sparser
"USP8 mutations disrupt the interaction between USP8 and the 14-3-3 protein, thereby allowing USP8 cleavage and increased enzymatic activity ( xref ); this protects EGFR from lysosomal degradation, which leads to increased expression of EGFR ( xref ) ( xref ) and pro-opiomelanocortin ( POMC) ( xref , xref )."
reach
"On the contrary, cytotoxic T lymphocytes (CTLs) play tumor-killing roles in the TME, and it is illustrated to be activated by an application of the USP8 inhibitor along with anti-PD-L1 agents because inhibition of USP8 could prevent PD-L1 from proteasome degradation (Yang et al., 2023)."
reach
"The results found that lncRNA SNHG12 downregulation led to reduced tumor volume and weight (P < 0.01, Fig. 9A, B) and Ki67 positive rate, and increased CD8 positive rate (P < 0.01, Fig. 9C), along with reduced levels of SNHG12, PD-L1, and USP8 (P < 0.01, Fig. 9D), elevated ubiquitination level of PD-L1 (P < 0.01, Fig. 9E), and decreased positive rate PD-L1 and USP8 (P < 0.01, Fig. 9F)."
sparser
"USP8 mutations disrupt the interaction between USP8 and the 14-3-3 protein, thereby allowing USP8 cleavage and increased enzymatic activity ( xref ); this protects EGFR from lysosomal degradation, which leads to increased expression of EGFR ( xref ) ( xref ) and pro-opiomelanocortin ( POMC) ( xref , xref )."
USP8 affects cell population proliferation
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54
1
USP8 activates cell population proliferation.
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37
USP8 activates cell population proliferation. 10 / 37
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37
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."
USP8 inhibits cell population proliferation.
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17
1
USP8 inhibits cell population proliferation. 10 / 18
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17
1
reach
"These chalcone derivatives effectively inhibit the activity of DUB, such as USP5, UCH-L3, USP2, UCH-L1, and USP8, leading to irreversible cell cycle arrest in breast, ovarian, and cervical cancer cells (IC50 = 1.5-12.5 µM), as well as inhibiting their proliferation and initiating apoptosis."
sparser
"Several lines of evidence suggest that the ubiquitin pathway regulates Smo endocytic trafficking and degradation: (1) Smo was accumulated in mutant clones lacking the ubiquitin-activating enzyme Uba1 in wing imaginal discs, and inactivation of Uba1 in S2 cells inhibited Smo ubiquitination and promoted its cell surface accumulation; (2) Smo was accumulated when the activity of several endocytic components or lysosome was inhibited; (3) Hh and PKA/CK1-mediated Smo phosphorylation inhibited Smo ubiquitination and increased Smo cell surface expression; (4) the Smo autoinhibitory domain (SAID) promoted receptor ubiquitination and internalization; (5) Smo was ubiquitinated at multiple sites both inside and outside the SAID domain and mutating the ubiquitin acceptor sites in SAID increased Smo half-life and cell surface expression; and (6) Smo cell surface expression was promoted by the deubiquitinating enzyme UBPY that binds Smo and counteracts Smo ubiquitination."
USP8 affects apoptotic process
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6
41
1
USP8 inhibits apoptotic process.
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5
27
1
USP8 inhibits apoptotic process. 10 / 34
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5
27
1
reach
"USP8 prevents extrinsic apoptosis, initiated by the ligation of anti-FAS antibody, TNF, or TNFSF10 to their specific receptors, through the direct deubiquitylation and stabilization of CFLAR rather than regulating the expression or surface availability of death receptors in cervical cancer and melanoma cells [16]."
reach
"Our results are also consistent with the finding that USP8 inhibits extrinsic apoptosis because when using the most efficient siRNA i.e., siRNA b to inhibit USP8, cisplatin-induced caspase 8 activation was evident.Molecular targeting of USP8 was also carried out in the IGROV-1 parental cell line and in the PEO1 cells."
USP8 activates apoptotic process.
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1
14
USP8 activates apoptotic process. 10 / 15
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1
14
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."
sparser
"Consistent with previous reports that USP8 regulates Parkin-mediated mitophagy by removing K6-linked ubiquitin chains, which facilitates Parkin translocation to damaged mitochondria [ xref , xref ], USP8 binds to Parkin in osteoclasts and stabilizes it through deubiquitination-dependent mechanism."
reach
"USP8 KD delayed but not fully abolished Parkin translocation and mitophagy without affecting mitochondrial membrane potential, steady-state levels of PINK1, PINK1 accumulation on mitochondria, mitochondrial protein levels and ubiquitination, or mitochondrial morphology, fusion, fission, and fragmentation [50]."
reach
"Parkin is in turn regulated by several DUBs; USP8 promotes Parkin activity and mitophagy by removing the K6-linked ubiquitin chains, which prevent Parkin’s interaction with the phosphorylated ubiquitin and PINK1 [157], while USP15 and USP30 antagonize Parkin by removing ubiquitin chains from mitochondria, preventing the binding of mitophagy receptors [158,159]."
reach
"These approaches allowed identifying a mitophagic effect of USP8 down-regulation, which was clearly detectable in vivo in the fly brain and also in neurons of human origin.Interestingly, USP8 down-regulation promoted basal mitophagy in a Parkin-independent fashion (Figure 2D,E), whereas it inhibited Parkin mitochondrial translocation and mitophagy under stress condition (Supplementary Figure S3)."
reach
"A study has shown that under the conditions of high glucose and high fat in vivo and in vitro, the S-sulfhydrylation of USP8 was significantly reduced, while after exogenous H S treatment, the S-sulfhydrylation level of USP8 was increased, promoting the combination of USP8 and Parkin."
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 )."
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 )."
"<span class="match term0">UBPY</span> 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 <span class="match term1">STAM</span>, by reversing their ubiquitination."
USP8 affects Neoplasm Invasiveness
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1
40
USP8 activates Neoplasm Invasiveness.
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1
38
USP8 activates Neoplasm Invasiveness. 10 / 36
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1
35
USP8 activates Neoplasm Invasiveness. 3 / 3
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3
USP8 inhibits Neoplasm Invasiveness.
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2
USP8 inhibits Neoplasm Invasiveness. 2 / 2
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2
reach
"In our study, we demonstrated that USP8 inhibition in combination with the ferroptosis inducer, SAS, significantly retarded the tumor growth and promoted the CD8 T cell infiltration in the tumor microenvironment, thereby enhancing the effectiveness of anti-PD-1 immunotherapy in multiple mouse tumor models."
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 )."
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 )."
reach
"Since proper folding of proteins generally devotes to their interactions with other partners (54), like the WD40 protein Bub3 (55), we thus suggest that the interaction of Hsp70 with Fzr facilitates proper folding of Fzr, thereby enhancing the interaction of Fzr with USP8 to promote Fzr deubiquitination and stabilization during endoreplication."
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."
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 clarify whether impaired ubiquitination affected the Clec16a-Nrdp1-USP8 complex as a result of reduced levels of constituents or by impaired complex assembly, we also doubled the amount of Flag-Clec16a plasmid in the presence of KO ubiquitin, resulting in increased levels of Clec16a, USP8, and Nrdp1 (Fig. 4E, lane ++)."
reach
"Collectively, these findings suggest that functional ubiquitination is necessary for maintaining levels of the constituents of the Clec16a-Nrdp1-USP8 complex as well as providing vital signals for complex assembly.USP8 shares functional overlap with Clec16a/Nrdp1 in the regulation of mitophagic flux, coinciding in their opposing regulation of the E3 ligase Parkin, a critical effector in mitophagy (34)."
reach
"These results suggest, again, that Clec16a drives assembly of the Clec16a-Nrdp1-USP8 complex by providing essential ubiquitin signals and stabilizing its component proteins.To determine whether the Clec16a-Nrdp1-USP8 axis regulates β-cell function, we assessed the role of Clec16a-mediated ubiquitination on GSIS in Min6 β-cells."
reach
"We found that depletion of USP8 markedly decreased OGT levels without influence on its mRNA abundance (Figure
5A), and the decrease could be reversed by the addition of proteasome inhibitor MG132 or overexpression wild‐type (WT) USP8, but not its catalytically inactive mutant (USP8‐C786A) (Figure 5B,C)."
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."
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 clarify whether impaired ubiquitination affected the Clec16a-Nrdp1-USP8 complex as a result of reduced levels of constituents or by impaired complex assembly, we also doubled the amount of Flag-Clec16a plasmid in the presence of KO ubiquitin, resulting in increased levels of Clec16a, USP8, and Nrdp1 (Fig. 4E, lane ++)."
reach
"Collectively, these findings suggest that functional ubiquitination is necessary for maintaining levels of the constituents of the Clec16a-Nrdp1-USP8 complex as well as providing vital signals for complex assembly.USP8 shares functional overlap with Clec16a/Nrdp1 in the regulation of mitophagic flux, coinciding in their opposing regulation of the E3 ligase Parkin, a critical effector in mitophagy (34)."
reach
"These results suggest, again, that Clec16a drives assembly of the Clec16a-Nrdp1-USP8 complex by providing essential ubiquitin signals and stabilizing its component proteins.To determine whether the Clec16a-Nrdp1-USP8 axis regulates β-cell function, we assessed the role of Clec16a-mediated ubiquitination on GSIS in Min6 β-cells."
1
1
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9
15
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."
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."
"Based on these observations, we propose that <span class="match term1">CHMP1B</span> is dynamically regulated by ubiquitination in response to EGF and that <span class="match term0">USP8</span> triggers <span class="match term1">CHMP1B</span> deubiquitination possibly favoring its subsequent assembly into a membrane-associated ESCRT-III polymer."
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]."
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 ferroptosis
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1
20
USP8 inhibits ferroptosis.
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1
15
USP8 inhibits ferroptosis. 10 / 16
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1
15
reach
"Collectively, this study demonstrates that pharmacological inhibition or knockout of USP8 can inhibit the progression of HCC and induce ferroptosis via decreasing the stability of OGT, which imposes a great challenge that targeting of USP8 is a potential approach for HCC treatment."
USP8 activates ferroptosis.
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5
USP8 activates ferroptosis. 5 / 5
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5
reach
"Immunohistochemistry (IHC) analysis of the expression of prostaglandin-endoperoxide synthase-2 (PTGS2), a marker for the assessment of oxidative stress and ferroptosis in vivo, indicated the combination effect of knocking down USP8 and erastin treatment in triggering tumor ferroptosis in vivo (Fig. 1L)."
reach
"Moreover, we constructed SQSTM1 knockdown HepG2 cells as control, shSQSTM1 cells were resistant to elastin-induced ferroptosis, and knockdown of ATG7 or SQSTM1 greatly reduced the sensitivity of the shUSP8 MEF cells to erastin-induced ferroptosis and decreased lipid ROS level (Fig. 2C and 2D), while reconstituting SQSTM1 in shUSP8/shSQSTM1 MEF cells partially restored cellular ferroptosis sensitivity (Fig. 2D), indicating USP8-mediated ferroptosis is an autophagy-dependent process involving SQSTM1 participation.As two important marker proteins of ferritinophagy, nuclear receptor coactivator 4 (NCOA4) and FTL are always degraded under ferroptosis, which may be regulated by SQSTM1."
USP8 affects Neoplasm Metastasis
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4
16
USP8 activates Neoplasm Metastasis.
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4
14
USP8 activates Neoplasm Metastasis. 10 / 18
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4
14
reach
"Notably, accumulating evidence suggests that upregulated or mutated USP8 can lead to cancer progression, metastasis, and poor survival by affecting multiple signaling pathways in different types of tumors, including, but not limited to, lung [19], gastric [20], and breast cancers [21, 22]."
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 Neoplasm Metastasis.
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2
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
"Thus, important prerequisites for compound optimization and drug development exist for USP8 and can be readily exploited in aged-associated neurodegenerative disease models.In summary, in this work we show that we can enhance autophagy and mitophagy by down-regulating USP8, a DUB that is upregulated in age-related neurodegenerative conditions [19,42]."
reach
"Interestingly, USP8 also enhances the interaction between EPG5 and LC3 in embryonic stem cells (EPCs), where EPG5 is a novel candidate for regulating autophagy in these cells (Gu et al., 2019); the knockdown of USP8 decreased the autophagy flux, while USP8 overexpression caused an increase in autophagy under normal and starvation conditions (Gu et al., 2019)."
reach
"Autophagy promotes tumor progression at advanced stages of tumor development, and USP8 negatively regulates the autophagy by deubiquitinating p62 (SQSTM1) at K420 [36,[50], [51], [52]], supposing that USP8 may be negatively implicated in the tumor progression via the regulation of autophagy."
reach
"These results suggest that the CCL5 gene is activated in an NF-κB–dependent manner in USP8-depleted cells.Since USP8 depletion causes the accumulation of K63 ubiquitin chains on endosomes, we hypothesized that the K63 ubiquitin signals directly activate NF-κB via ubiquitin decoders."
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."
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."
USP8 affects autophagy of mitochondrion
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18
USP8 activates autophagy of mitochondrion.
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13
USP8 activates autophagy of mitochondrion. 10 / 13
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13
reach
"Thus, important prerequisites for compound optimization and drug development exist for USP8 and can be readily exploited in aged-associated neurodegenerative disease models.In summary, in this work we show that we can enhance autophagy and mitophagy by down-regulating USP8, a DUB that is upregulated in age-related neurodegenerative conditions [19,42]."
reach
"In summary, high expression of USP8 may promote the occurrence of mitophagy through the TGF‐β signaling pathway, thereby reducing the number of CD4 naïve T cells, which needs further confirmation.CDKN2B (Cyclin‐dependent kinase 4 inhibitor B) is a potent inhibitor of various tumors, which can inhibit the TGF‐β‐mediated cell cycle, and was also enriched in the TGF‐β signaling pathway of the hub genes."
reach
"Parkin is in turn regulated by several DUBs; USP8 promotes Parkin activity and mitophagy by removing the K6-linked ubiquitin chains, which prevent Parkin’s interaction with the phosphorylated ubiquitin and PINK1 [157], while USP15 and USP30 antagonize Parkin by removing ubiquitin chains from mitochondria, preventing the binding of mitophagy receptors [158,159]."
reach
"These approaches allowed identifying a mitophagic effect of USP8 down-regulation, which was clearly detectable in vivo in the fly brain and also in neurons of human origin.Interestingly, USP8 down-regulation promoted basal mitophagy in a Parkin-independent fashion (Figure 2D,E), whereas it inhibited Parkin mitochondrial translocation and mitophagy under stress condition (Supplementary Figure S3)."
USP8 inhibits autophagy of mitochondrion.
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5
USP8 inhibits autophagy of mitochondrion. 5 / 5
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5
reach
"In these neurons of human origin, we found that USP8 pharmacological inhibition by DUBs-IN-2 (0.5–1 μM/24–48 h) enhances basal mitophagy, an effect that was comparable to 0.5 μM antimycin/oligomycin (AO) treatment, which we used as positive control for mitophagy induction (Figure 4C)."
reach
"These approaches allowed identifying a mitophagic effect of USP8 down-regulation, which was clearly detectable in vivo in the fly brain and also in neurons of human origin.Interestingly, USP8 down-regulation promoted basal mitophagy in a Parkin-independent fashion (Figure 2D,E), whereas it inhibited Parkin mitochondrial translocation and mitophagy under stress condition (Supplementary Figure S3)."
USP8 affects Carcinogenesis
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1
17
sparser
"Given our most recent studies indicating that HUR protein binds to USP8 mRNA and stabilizes USP8 mRNA [ xref ], and lncRNAs binds to their targeted protein and affects their bound protein function [ xref – xref ], we further probed the potential interaction between SNHG1 and HUR protein and the data obtained from the online analyses using catRAPID, RPISeq, StarBase V2.0 did suggest their interaction."
USP8 affects cell growth
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14
USP8 activates cell growth. 10 / 17
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14
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
"DUB-IN-1 and its analogs inhibited the growth of colon and prostate cancer cells, with IC s ranging 0.5–1.5 µM. Novel USP8 inhibitors were further discovered and exhibited anticancer efficiency, and treatment with the USP8 inhibitor or siRNA targeting USP8 was reported to inhibit HER-3-positive gastric cancer cell growth [14]."
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]."
sparser
"Consistent with previous reports that USP8 regulates Parkin-mediated mitophagy by removing K6-linked ubiquitin chains, which facilitates Parkin translocation to damaged mitochondria [ xref , xref ], USP8 binds to Parkin in osteoclasts and stabilizes it through deubiquitination-dependent mechanism."
USP8 affects inflammatory response
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15
USP8 inhibits inflammatory response.
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8
USP8 inhibits inflammatory response. 8 / 8
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8
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"In liver fibrosis models and activated Kupffer cells (KCs), the elevated expression of METTL3 enhances metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) levels via m6A methylation and facilitates the degradation of ubiquitin-specific peptidase 8 (USP8) mRNA, subsequently reduces transforming growth factor β-activated kinase 1 (TAK1) regulation, enhances cell pyroptosis markers (NLRP3, caspase-1, GSDMD-N) and NF-κB p-p65 levels, thereby promoting macrophage pyroptosis and inflammation [58]."
USP8 activates inflammatory response.
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7
USP8 activates inflammatory response. 7 / 7
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7
reach
"In liver fibrosis models and activated Kupffer cells (KCs), the elevated expression of METTL3 enhances metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) levels via m6A methylation and facilitates the degradation of ubiquitin-specific peptidase 8 (USP8) mRNA, subsequently reduces transforming growth factor β-activated kinase 1 (TAK1) regulation, enhances cell pyroptosis markers (NLRP3, caspase-1, GSDMD-N) and NF-κB p-p65 levels, thereby promoting macrophage pyroptosis and inflammation [58]."
reach
"OTUD4 and Cezanne remove K63-linked polyubiquitin chains on tumour necrosis factor receptor-associated factor 6 (TRAF6), alleviating inflammation and IRI in the liver and kidney respectively [144,145], and USP8 alleviates intermittent hypoxia/reoxygenation induced inflammation by removing K63-linked ubiquitination of TAK1 [146]."
USP8 affects docetaxel anhydrous
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2
13
USP8 inhibits docetaxel anhydrous.
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2
11
USP8 inhibits docetaxel anhydrous. 10 / 13
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2
11
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."
USP8 activates docetaxel anhydrous.
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2
reach
"Conversely, inhibition of USP8 by genetic ablation or its pharmacological inhibitor (DUB-IN-2) down-regulates GPX4, sensitizing tumor cells to ferroptosis, retarding tumor growth, and increasing tumor-infiltrating CD8 T cells that potentiates the PD-1/PD-L1 blockade therapy (SI Appendix, Fig. S6 E, Right)."
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."
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."
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."
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."
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."
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
"Given our most recent studies indicating that HUR protein binds to USP8 mRNA and stabilizes USP8 mRNA [ xref ], and lncRNAs binds to their targeted protein and affects their bound protein function [ xref – xref ], we further probed the potential interaction between SNHG1 and HUR protein and the data obtained from the online analyses using catRAPID, RPISeq, StarBase V2.0 did suggest their interaction."
"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)."
"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)."
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
"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 )."
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
"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 )."
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)."
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) ."
USP8 affects BRIT1
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12
USP8 deubiquitinates BRIT1.
|
6
USP8 binds BRIT1.
|
6
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
"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]."
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."
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."
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."
USP8 affects signal transduction
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10
USP8 activates signal transduction.
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7
USP8 activates signal transduction. 7 / 7
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7
reach
"Inhibiting USP8 impairs TGF-β/SMAD signal transduction, leading to reduced stability of the β receptor II (βRII) and a decreased quantity of TβRII + circulating extracellular vesicles (crEVs), which in turn diminishes CD8 + T-cell exhaustion and reinstates anti-tumor responses [56]."
USP8 inhibits signal transduction.
|
3
"Here, we report that RNAi-mediated depletion of USP8 reduced levels of both ectopically expressed and endogenous BACE1 in H4 human neuroglioma cells. Moreover, USP8 depletion increased BACE1 ubiquitination, promoted BACE1 accumulation in the early endosomes and late endosomes/lysosomes, and decreased levels of BACE1 in the recycling endosomes."
"The Endosome-associated Deubiquitinating Enzyme <span class="match term0">USP8</span> Regulates <span class="match term1">BACE1</span> Enzyme Ubiquitination and Degradation"
"Here, we report that RNAi-mediated depletion of USP8 reduced levels of both ectopically expressed and endogenous BACE1 in H4 human neuroglioma cells. Moreover, USP8 depletion increased BACE1 ubiquitination, promoted BACE1 accumulation in the early endosomes and late endosomes/lysosomes, and decreased levels of BACE1 in the recycling endosomes."
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) ."
USP8 increases the amount of USP8.
|
5
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)."
USP8 decreases the amount of USP8.
|
1
USP8 activates USP8.
|
1
reach
"The results found that lncRNA SNHG12 downregulation led to reduced tumor volume and weight (P < 0.01, Fig. 9A, B) and Ki67 positive rate, and increased CD8 positive rate (P < 0.01, Fig. 9C), along with reduced levels of SNHG12, PD-L1, and USP8 (P < 0.01, Fig. 9D), elevated ubiquitination level of PD-L1 (P < 0.01, Fig. 9E), and decreased positive rate PD-L1 and USP8 (P < 0.01, Fig. 9F)."
reach
"The ubiquitination of TRAF6 could be seen in the absence of Myc-USP8 (Fig. 1E, lane 2), whereas the marked deubiquitination of TRAF6 was observed in the presence of Myc-USP8 in a dose-dependent manner (Fig. 1E, lane 3–5), indicating that USP8 induces the deubiquitination of TRAF6, as depicted in Fig. 1F."
reach
"Based on the findings that USP8 induced the deubiquitination of TRAF6-associated proteins, such as TRAF6, TAK1 (MAP3K7), TAB2, BECN1, and p62 (SQSTM1), for the activation of NF-κB and autophagy in response to TLR4, the GEPIA database was used to analyze the correlation between USP8 and these genes in the normal and LIHC cells."
sparser
"In addition, USP8 interacted with Flag-wild type (WT) TRAF6, Flag-TRAF6 110- 522 truncated mutant, and Flag-TRAF6 260-522 truncated mutant ( xref B, TRAF6 truncated mutants; xref C, lanes 6–8), whereas there was no significant interaction with Flag-TRAF6 349-522 truncated mutant ( xref C, lane 9), indicating that USP8 interacts with the coiled-coil domain of TRAF6 ( xref D)."
USP8 affects Stomach Neoplasms
|
9
USP8 inhibits Stomach Neoplasms.
|
6
USP8 activates Stomach Neoplasms.
|
3
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."
reach
"An analysis of survival-related features of the cisplatin-resistant IGROV-1/Pt1 cells upon USP8 molecular targeting, indicated that USP8 interplays with RTKs since its silencing resulted in reduced activation of all RTKs belonging to the Human Epidermal Growth Factor Receptor (HER) family i.e., ErbB1/EGF-R, ErbB2, ErbB3 and ErbB4, and as a consequence decreased Akt activation as shown by reduced phosphorylation at Ser473."
reach
"Our findings are in keeping with the latter report and the view that reduced USP8 level may decrease activation of RTKs and as a consequence of the downstream PI3K/Akt pathway.Molecular targeting of USP8 revealed a link between FLIP and USP8, with down-regulation of FLIP upon USP8 silencing resulting in enhanced susceptibility to cisplatin-induced apoptosis as observed by Annexin V-binding assays in USP8-silenced cells."
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 ) ."
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
"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
"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."
reach
"The results of this study suggest that inhibiting USP8 promotes the degradation of FGFR2 via the proteasome, leading to suppression of STAT3 signaling in ARID1A-deficient OCCCs and subsequent induction of apoptosis.Since approximately half of OCCCs carry ARID1A-deficient mutations, synthetic lethal therapy using the USP8 inhibitors identified in this study could become a crucial personalized treatment approach."
reach
"Then, suppression of USP8 explicitly promotes the degradation of FGFR2 in ARID1A-deficient cells, and the STAT3 pathway, which is its downstream pathway, was suppressed, resulting in synthetic lethality by induction of apoptosis.ARID1A-deficient cancers include a significant number of gastric cancers, biliary tract cancers, and pancreatic cancers ."
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."
Sulforaphane affects USP8
|
5
2
USP8 affects cell migration
|
7
USP8 activates cell migration. 7 / 7
|
7
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
)."
sparser
"Further studies show CHMP5 binds USP8 in CD69 + TCRβ hi DP cells but not in CD69 − TCRβ neg-lo DP cells, which have not undergone positive selection, suggesting that positive selection induces USP8-CHMP5 interaction, thus CHMP5 is deubiquitinated and stabilized, enabling CHMP5 to inhibit oxidation and degradation of Bcl-2, thereby promoting survival of positively selected thymocytes ( xref )."
reach
"Further studies show CHMP5 binds USP8 in CD69 TCRβ DP cells but not in CD69 TCRβ DP cells, which have not undergone positive selection, suggesting that positive selection induces USP8-CHMP5 interaction, thus CHMP5 is deubiquitinated and stabilized, enabling CHMP5 to inhibit oxidation and degradation of Bcl-2, thereby promoting survival of positively selected thymocytes (105)."
reach
"The results found that lncRNA SNHG12 downregulation led to reduced tumor volume and weight (P < 0.01, Fig. 9A, B) and Ki67 positive rate, and increased CD8 positive rate (P < 0.01, Fig. 9C), along with reduced levels of SNHG12, PD-L1, and USP8 (P < 0.01, Fig. 9D), elevated ubiquitination level of PD-L1 (P < 0.01, Fig. 9E), and decreased positive rate PD-L1 and USP8 (P < 0.01, Fig. 9F)."
reach
"The results found that lncRNA SNHG12 downregulation led to reduced tumor volume and weight (P < 0.01, Fig. 9A, B) and Ki67 positive rate, and increased CD8 positive rate (P < 0.01, Fig. 9C), along with reduced levels of SNHG12, PD-L1, and USP8 (P < 0.01, Fig. 9D), elevated ubiquitination level of PD-L1 (P < 0.01, Fig. 9E), and decreased positive rate PD-L1 and USP8 (P < 0.01, Fig. 9F)."
sparser
"Further studies show CHMP5 binds USP8 in CD69 + TCRβ hi DP cells but not in CD69 − TCRβ neg-lo DP cells, which have not undergone positive selection, suggesting that positive selection induces USP8-CHMP5 interaction, thus CHMP5 is deubiquitinated and stabilized, enabling CHMP5 to inhibit oxidation and degradation of Bcl-2, thereby promoting survival of positively selected thymocytes ( xref )."
reach
"Further studies show CHMP5 binds USP8 in CD69 TCRβ DP cells but not in CD69 TCRβ DP cells, which have not undergone positive selection, suggesting that positive selection induces USP8-CHMP5 interaction, thus CHMP5 is deubiquitinated and stabilized, enabling CHMP5 to inhibit oxidation and degradation of Bcl-2, thereby promoting survival of positively selected thymocytes (105)."
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."
USP8 affects localization
|
6
USP8 inhibits localization.
|
3
USP8 inhibits localization. 3 / 3
|
3
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]."
USP8 activates localization.
|
3
|
6
USP8 activates epithelial to mesenchymal transition. 6 / 6
|
6
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."
USP8 affects cilium assembly
|
1
5
USP8 inhibits cilium assembly.
|
1
3
USP8 activates cilium assembly.
|
2
USP8 affects cell cycle
|
1
5
USP8 affects N-HER2
|
6
reach
"PAK5 promotes the recruitment of USP8 for N-HER2 to inhibit N-HER2 ubiquitination degradation thought lncRNA MALAT1, leading to N-HER2 accumulation.N -methyladenosine (m A) modifications, the most prevalent form of epigenetic modification in RNA, intricately linked to cell proliferation, metastasis, metabolism, and therapeutic resistance [22]."
reach
"The upregulated MALAT1 enhances the binding between USP8 and N-HER2, inhibiting the N-HER2 ubiquitin proteasomal degradation and promoting N-HER2 accumulation, PAK5 induces HER2 accumulation by inhibiting N-HER2 ubiquitination degradation via stabilization of MALAT1, which occurs through PAK5-mediated phosphorylation of METTL14, thereby playing a crucial role in breast cancer targeted trastuzumab resistance.Although previous results suggest promoting function for PAK5 in breast cancer, definitive evidence related to drug resistance in breast cancer has been lacking until this study was performed."
USP8 affects MHC-I
|
1
5
reach
"However, the observation that USP8 and USP48 rather positively regulate HH signaling, whereas GNAS, MEN1, PRKAR1A, DICER1 and VHL rather negatively regulate this signaling pathway in PitNETs, does not allow a definitive conclusion, whether it is active or inactive HH signaling that is involved in formation of these tumors."
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 Deubiquitinase
|
6
USP8 inhibits Deubiquitinase.
|
4
USP8 activates Deubiquitinase.
|
2
USP8 affects Cell Survival
|
6
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."
N-HER2 affects USP8
|
6
reach
"PAK5 promotes the recruitment of USP8 for N-HER2 to inhibit N-HER2 ubiquitination degradation thought lncRNA MALAT1, leading to N-HER2 accumulation.N -methyladenosine (m A) modifications, the most prevalent form of epigenetic modification in RNA, intricately linked to cell proliferation, metastasis, metabolism, and therapeutic resistance [22]."
reach
"The upregulated MALAT1 enhances the binding between USP8 and N-HER2, inhibiting the N-HER2 ubiquitin proteasomal degradation and promoting N-HER2 accumulation, PAK5 induces HER2 accumulation by inhibiting N-HER2 ubiquitination degradation via stabilization of MALAT1, which occurs through PAK5-mediated phosphorylation of METTL14, thereby playing a crucial role in breast cancer targeted trastuzumab resistance.Although previous results suggest promoting function for PAK5 in breast cancer, definitive evidence related to drug resistance in breast cancer has been lacking until this study was performed."
MALAT1 affects USP8
|
6
MALAT1 inhibits USP8.
|
4
reach
"In this study, we showed that MALAT1, through the direct interaction with PTBP1, promoted the degradation of USP8 mRNA and inhibited USP8-mediated regulation of TAK1 protein.As an RNA-binding protein and a splicing factor, PTBP1 may activate or repress the transcription of a target gene, by regulating pre-mRNA splicing, polyadenylation, mRNA stability, and/or translation initiation [31]."
MALAT1 binds USP8.
|
2
BRIT1 affects USP8
|
6
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
"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
"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 affects degradation
|
5
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 "
USP8 affects corticotropin secretion
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5
USP8 activates corticotropin secretion. 3 / 3
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3
Mutated USP8 activates corticotropin secretion. 2 / 2
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2
reach
"In this respect, further studies investigating the roles of USPs in UPS are required.Hyperactive mutations of Usp8 and Usp48 cause excessive ACTH secretion from corticotroph adenomas, implying that USP8 and 48 have the potential to modulate the hypothalamus-pituitary-adrenal axis under physiological conditions."
sparser
"Collectively, these findings position DUBs as master regulators of neuroinflammatory and neuroprotective responses in CIRI, operating through: (i) direct ubiquitin code editing of inflammasome components (BRCC3-NLRP6, CYLD-NLRP3), (ii) multi-layered control of NF-κB signaling (A20/TRAF6, CYLD-TRAF2/6, OTUD1/RIP2, USP25/TAB2), (iii) dynamic modulation of microglial polarization states (USP8-TLR4, USP14-REST), and critically, (iv) axonal integrity preservation via UCHL1-mediated stabilization of synaptic scaffolds (PSD-95/neurofilaments), offering a compelling therapeutic paradigm for targeted immunomodulation in IS."
reach
"Furthermore, in a previous study, USP8 increased NRDP1 levels, potently downregulated MyD88 and TLR4 levels, and blocked inhibitor of NF-κB kinase subunit β and IκBα phosphorylation, thus decreasing p65 nuclear translocation, resulting in and inhibition of NF-κB signaling pathway activation in LPS-induced mice (12)."
"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)."
"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)."
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 )."
SNHG1 affects USP8
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5
reach
"The results showed that ectopic expression of SNHG1 dramatically attenuated the USP8 mRNA level that was precipitated by the anti-HUR antibody in comparison to its scramble vector transfectant (Fig. 8D), suggesting that negative correlation of SNHG1 expression and USP8 mRNA expression.In our quest to conclusively demonstrate that SNHG1 influence over downstream genes and cellular behaviors hinges on HUR, we had successfully engineered shHUR into U5637(Vector) and U5637(SNHG1) for the targeted knockdown of HUR, as illustrated in Fig. 8E."
USP8 affects regulation of cell cycle
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4
USP8 affects proteolysis
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4
USP8 affects lipopolysaccharide
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4
sparser
"The ubiquitination of TRAF6 could be seen in the absence of Myc-USP8 ( xref E, lane 2), whereas the marked deubiquitination of TRAF6 was observed in the presence of Myc-USP8 in a dose-dependent manner ( xref E, lane 3–5), indicating that USP8 induces the deubiquitination of TRAF6, as depicted in xref F. The ubiquitinated TRAF6 is associated with the TAK1-TAB1-TAB2 complex and induces the ubiquitination of TAB2 and TAK1, leading to the activation of NF-κB [ xref , xref , xref ]."
USP8 affects E3_Ub_ligase
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4
sparser
"Two of the four in vitro sensitive tumors (−17.1 ± 5.7% and −29.3 ± 1.1% secretion vs. basal for tumors #1 and #2, respectively, p < 0.05) were transiently transfected with S718del USP8 mutant while the remaining two in vitro sensitive tumors (−38.2 ± 2% and −22.7 ± 3.5% secretion vs. basal for tumors #4 and #5, respectively, p < 0.05) with the C40-USP8 mutant."
reach
"In this study, we confirmed the interaction between USP8 and ASCL1 by Co-IP results and increased ubiquitination of ASCL1 after knockdown of USP8.Previous studies have found that CD47 is involved in osteoblast and stromal cell/osteoblast differentiation in mouse bone marrow cultures and that a lack of CD47 severely impairs SIRPα-dependent osteoblast differentiation and leads to a reduction in osteoclast formation (Koskinen et al. 2013)."
RA-9 affects USP8
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4
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"The ubiquitination of TRAF6 could be seen in the absence of Myc-USP8 ( xref E, lane 2), whereas the marked deubiquitination of TRAF6 was observed in the presence of Myc-USP8 in a dose-dependent manner ( xref E, lane 3–5), indicating that USP8 induces the deubiquitination of TRAF6, as depicted in xref F. The ubiquitinated TRAF6 is associated with the TAK1-TAB1-TAB2 complex and induces the ubiquitination of TAB2 and TAK1, leading to the activation of NF-κB [ xref , xref , xref ]."
Deubiquitinase affects USP8
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4
Deubiquitinase inhibits USP8.
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2
Deubiquitinase inhibits USP8. 2 / 2
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2
Deubiquitinase activates USP8.
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2
sparser
"Two of the four in vitro sensitive tumors (−17.1 ± 5.7% and −29.3 ± 1.1% secretion vs. basal for tumors #1 and #2, respectively, p < 0.05) were transiently transfected with S718del USP8 mutant while the remaining two in vitro sensitive tumors (−38.2 ± 2% and −22.7 ± 3.5% secretion vs. basal for tumors #4 and #5, respectively, p < 0.05) with the C40-USP8 mutant."
reach
"In this study, we confirmed the interaction between USP8 and ASCL1 by Co-IP results and increased ubiquitination of ASCL1 after knockdown of USP8.Previous studies have found that CD47 is involved in osteoblast and stromal cell/osteoblast differentiation in mouse bone marrow cultures and that a lack of CD47 severely impairs SIRPα-dependent osteoblast differentiation and leads to a reduction in osteoclast formation (Koskinen et al. 2013)."
Trichoplein affects USP8
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3
Lipopolysaccharide affects USP8
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3
Bisphenol A affects USP8
3
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USP8 affects trichoplein
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3
USP8 affects glutathione
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3
USP8 affects condensation
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3
USP8 affects cell death
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3
USP8 affects TGF-β/SMAD
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3
reach
"Thus, the potential influence of baseline radiotherapy treatment on the subsequent improved response to pasireotide LAR therapy cannot be entirely excluded.Ubiquitin-specific protease 8 (USP-8) gene mutational status could be a potential marker of the pasireotide response, as mutant USP8 forms may upregulate SSTR5 transcription [1,17,18]."
USP8 affects SAIT301
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3
USP8 affects Rabx5
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3
USP8 affects Pituitary ACTH Hypersecretion
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2
USP8 activates Pituitary ACTH Hypersecretion. 2 / 3
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2
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 ."
sparser
"We then examined the association between USP8 and MDA5 and found that USP8 specifically interacted with MDA5 but not with other related proteins, such as RIG‐I (Figure xref ; Figure xref , Supporting Information), and that their association was potentiated after EMCV infection, but not Poly(I:C) HMW (Figure xref ; Figure xref , Supporting Information)."
USP8 affects ESCRT-III
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3
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]."
sparser
"Collectively, these findings position DUBs as master regulators of neuroinflammatory and neuroprotective responses in CIRI, operating through: (i) direct ubiquitin code editing of inflammasome components (BRCC3-NLRP6, CYLD-NLRP3), (ii) multi-layered control of NF-κB signaling (A20/TRAF6, CYLD-TRAF2/6, OTUD1/RIP2, USP25/TAB2), (iii) dynamic modulation of microglial polarization states (USP8-TLR4, USP14-REST), and critically, (iv) axonal integrity preservation via UCHL1-mediated stabilization of synaptic scaffolds (PSD-95/neurofilaments), offering a compelling therapeutic paradigm for targeted immunomodulation in IS."
SJB3-019A affects USP8
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1
2
Rabx5 affects USP8
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3
sparser
"We then examined the association between USP8 and MDA5 and found that USP8 specifically interacted with MDA5 but not with other related proteins, such as RIG‐I (Figure xref ; Figure xref , Supporting Information), and that their association was potentiated after EMCV infection, but not Poly(I:C) HMW (Figure xref ; Figure xref , Supporting Information)."
Α-synuclein affects USP8
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1
Sodium arsenite affects USP8
2
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MiR-302a-3p affects USP8
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1
1
Indometacin affects USP8
2
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Hsa-mir-466 affects USP8
2
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Hsa-mir-4643 affects USP8
2
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Hsa-miR-95-5p affects USP8
2
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Hsa-miR-4789-3p affects USP8
2
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Hsa-miR-19b-3p affects USP8
2
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USP8 affects α-synuclein
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1
USP8 affects ubiquitination TrkB
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2
USP8 affects removal
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2
USP8 affects pyroptosis
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2
USP8 inhibits pyroptosis. 2 / 2
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2
reach
"In liver fibrosis models and activated Kupffer cells (KCs), the elevated expression of METTL3 enhances metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) levels via m6A methylation and facilitates the degradation of ubiquitin-specific peptidase 8 (USP8) mRNA, subsequently reduces transforming growth factor β-activated kinase 1 (TAK1) regulation, enhances cell pyroptosis markers (NLRP3, caspase-1, GSDMD-N) and NF-κB p-p65 levels, thereby promoting macrophage pyroptosis and inflammation [58]."
USP8 affects pemigatinib
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2
USP8 affects pathway
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2
USP8 affects pathogenesis
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2
USP8 affects neuregulin receptor
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2
USP8 affects immune response
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2
USP8 affects erastin
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2
reach
"These results indicated that USP8 may be a specific negative regulator of ferroptosis, instead of apoptosis or necrosis modulator.To confirm whether USP8 suppression enhances the anti-cancer activity of erastin in vivo, we stably knocked down USP8 in NCI-H1299 cell line by lentiviral vector."
USP8 affects endocytosis
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2
USP8 affects corticotropin
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2
USP8 affects cell differentiation
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2
USP8 affects cGAS-STING
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2
USP8 affects TrkB-dependent neuronal differentiation
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2
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 Parkinson Disease
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2
USP8 affects POMC promoter
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2
USP8 affects MALAT1
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2
USP8 affects LM3
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2
sparser
"In a prospective study, Meyer et al ( xref ) reported that a very small number of patients with acute leukemia have rearranged USP2 and USP8 genes and that the conserved region of the deubiquitinating enzyme ‘UCH-domain’ fuses to an extended 5´-MLL portion, which formed the fusion proteins MLL-USP2 and MLL-USP8."
USP8 affects Interferon
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2
USP8 affects Infections
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2
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2
USP8 affects ESCRT-III complex
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2
USP8 affects Death_receptor
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2
USP8 inhibits Death_receptor. 2 / 2
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2
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"Although in HeLa cells silencing USP8 promotes death receptor-mediated extrinsic apoptosis (47), here we found that USP8 affects apoptosis in PCa via modulating the intrinsic apoptosis pathway, and its influence on extrinsic apoptosis in PCa is needed to be investigated more in the future.EGFR has been studied as a potential target in various solid cancers, including lung, bladder, colon, breast, and head and neck carcinomas."
USP8 affects Carcinoma, Hepatocellular
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2
USP8 affects CHMP proteins
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2
USP8 affects CDH3
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2
reach
"In the present study, our study confirmed that after transfection with si-CD47, hBMSCs showed reduced levels of glucose consumption and decreased levels of ATP production, lactate production, ALP activity, and mineralized nodules.In summary, this study indicates that USP8 ubiquitination regulates ASCL1 expression and mediates CD47 transcriptional activation of the AKT signaling pathway and that glycolysis promotes osteogenic differentiation of hBMSCs."
USP8 affects Alzheimer Disease
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2
USP8 affects Ala-Gly-Ser
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2
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
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2
sparser
"In addition, USP8 interacted with Flag-wild type (WT) TRAF6, Flag-TRAF6 110- 522 truncated mutant, and Flag-TRAF6 260-522 truncated mutant ( xref B, TRAF6 truncated mutants; xref C, lanes 6–8), whereas there was no significant interaction with Flag-TRAF6 349-522 truncated mutant ( xref C, lane 9), indicating that USP8 interacts with the coiled-coil domain of TRAF6 ( xref D)."
SAIT301 affects USP8
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2
RNAi affects USP8
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2
Particulate Matter affects USP8
2
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sparser
"In a prospective study, Meyer et al ( xref ) reported that a very small number of patients with acute leukemia have rearranged USP2 and USP8 genes and that the conserved region of the deubiquitinating enzyme ‘UCH-domain’ fuses to an extended 5´-MLL portion, which formed the fusion proteins MLL-USP2 and MLL-USP8."
ESCRT-III complex affects USP8
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2
E3_Ub_ligase affects USP8
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2
DUBs-IN-2 affects USP8
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2
ChlA-F affects USP8
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2
CHMP proteins affects USP8
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2
CDH3 affects USP8
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2
AM146 affects USP8
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2
AIP4 affects USP8
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2