IndraLab

Statements

USP8 affects EGFR

18 1 | 2 18

USP8 deubiquitinates EGFR. 10 / 16

1 | 1 14

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

28959952

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

23333852

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"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]"

17720156

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"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."

23477725

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

29981430

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"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."

23049745

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

16702236

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ubibrowser

"Review"

27775833

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"Immunopurified UBPY deubiquitinated EGFR in vitro."

16120644

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"Gain-of-function mutations in USP8 increase the deubiquitination of EGFR, which inhibits its degradation, leading to the activation of EGFR signaling."

33574795

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

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biopax:pid

No evidence text available

17121848

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biopax:pid

No evidence text available

17052190

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biopax:pid

No evidence text available

16120644

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

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biopax:pid

No evidence text available

17121848

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biopax:pid

No evidence text available

17052190

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biopax:pid

No evidence text available

16120644

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

| 3

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

26285834

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"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."

36916541

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"USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells."

25942478

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

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biopax:pid

No evidence text available

16120644

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biopax:pid

No evidence text available

17121848

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biopax:pid

No evidence text available

17052190

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

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biopax:pid

No evidence text available

16120644

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biopax:pid

No evidence text available

17052190

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biopax:pid

No evidence text available

17121848

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

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biopax:pid

No evidence text available

17052190

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biopax:pid

No evidence text available

17121848

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biopax:pid

No evidence text available

16120644

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

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biopax:pid

No evidence text available

16120644

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biopax:pid

No evidence text available

17121848

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biopax:pid

No evidence text available

17052190

USP8 deubiquitinates EGFR-Y1045F. 1 / 1

| 1

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"The Cbl binding site mutants of EGFR (Y1045F) and EGFR-ErbB2 (Y1091F) are also deubiquitinated by Usp8 both with and without EGF stimulation (Figs. 7 and 8)."

21044682

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

| 1

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"We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes."

16120644

USP8 affects SMO

1 | 18

USP8 deubiquitinates SMO. 10 / 14

1 | 13

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

26120032

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"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."

22253573

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

22253573

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"Review"

27775833

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"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)."

26120032

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"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."

26973699

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"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."

26973699

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

22253573

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"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."

22253574

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"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."

22253574

Modified USP8 leads to the deubiquitination of SMO. 4 / 4

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"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)."

22253574

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

22253573

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"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."

22253573

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

22253573

Sumoylated USP8 leads to the deubiquitination of SMO. 1 / 1

| 1

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"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]."

31845722

USP8 affects EPG5

1 | 11

USP8 deubiquitinates EPG5. 10 / 12

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

30931944

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"USP8 regulates ESC identity through deubiquitinating EPG5."

30931944

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

30931944

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"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)."

30931944

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"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."

30931944

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

30931944

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

30931944

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"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."

30931944

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

30931944

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"USP8 deubiquitinates EPG5 by removing K63-ubiquitin chains."

30931944

USP8 affects PRKN

1 | 6

USP8 deubiquitinates PRKN. 7 / 7

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"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."

29934616

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"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."

32257541

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"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]."

25545884

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"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."

28408429

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

25216678

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

30988163

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"USP8 deubiquitylation of auto-ubiquitylated Parkin is required for its localization to depolarized mitochondria, and thereby for efficient activation of mitophagy [XREF_BIBR]."

26611876

USP8 affects CHMP1B

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USP8 deubiquitinates CHMP1B. 7 / 7

1 | 6

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

29933386

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"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."

29933386

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"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)."

29933386

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

29933386

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"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."

29933386

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

29933386

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"Our results thus strongly suggest that USP8 deubiquitinates CHMP1B."

29933386

USP8 affects BRIT1

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USP8 deubiquitinates BRIT1. 6 / 6

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"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."

26683461

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

26683461

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

25733871

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

27516771

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"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."

26683461

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"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."

26683461

Modified USP8 leads to the deubiquitination of BRIT1. 1 / 1

| 1

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"Loss of BRUCE or USP8 impairs BRIT1 deubiquitination, BRIT1 binding with gamma-H2AX, the formation of BRIT1 DNA damage foci, and chromatin relaxation."

25733871

USP8 affects LRIG1

1 1 | 3

USP8 deubiquitinates LRIG1. 3 / 3

1 | 2

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"Review"

28279784

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

24828152

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"Also, when over-expressed, USP8 decreases LRIG1 ubiquitination by SAIT301 treatment (XREF_FIG)."

24828152

USP8 deubiquitinates LRIG1 on lysine. 1 / 1

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biopax:reactome

No evidence text available

Modified USP8 leads to the deubiquitination of LRIG1. 1 / 1

| 1

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

24828152

USP8 affects CLOCK

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USP8 deubiquitinates CLOCK. 5 / 5

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"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."

23154984

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"Since deubiquitylation of CLK by USP8 decreases its activity XREF_BIBR, it will be interesting to investigate whether CK2alpha phosphorylation affects CLK ubiquitylation."

24013921

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"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."

23731779

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"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]."

23731779

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"CLOCK deubiquitylation by USP8 inhibits CLK and CYC transcription in Drosophila."

23154984

USP8 affects STAM

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USP8 deubiquitinates STAM. 4 / 4

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

26459808

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

33417828

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"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]."

23845989

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"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."

16996268

USP8 affects SQSTM1

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USP8 deubiquitinates SQSTM1. 4 / 4

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"USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR]."

33628391

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"USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR]."

33628391

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"USP8 overexpression leads to deubiquitination of p62 protein, suppressing its autophagic activity (Peng et al. 2020)."

34689261

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"USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction."

34688043

USP8 affects RNF41

1 1 | 2

USP8 deubiquitinates RNF41. 3 / 3

1 | 2

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"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."

20868762

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"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]."

23845989

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"Review"

27775833

Threonine-phosphorylated USP8 deubiquitinates RNF41. 1 / 1

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biopax:pid

No evidence text available

17210635

USP8 affects HGS

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USP8 deubiquitinates HGS. 4 / 4

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

24574010

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

26224310

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"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."

26973699

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"Previous studies showed that Hrs is deubiquitinated by Ubpy."

26224310

USP8 affects GJA1

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USP8 deubiquitinates GJA1. 4 / 4

1 | 3

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"USP8 reduces both multiple monoubiquitination and polyubiquitination of Cx43 to prevent autophagy mediated degradation."

29626091

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ubibrowser

"The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43"

29626091

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"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."

31501970

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"USP8 interacts with and deubiquitinates Cx43, removing monoubiquitin moieties as well as K63- and K48 linked ubiquitin chains."

30126257

USP8 affects SHANK3

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USP8 deubiquitinates SHANK3. 3 / 3

1 | 2

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"USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity Dependent Protein Levels."

29735556

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ubibrowser

"USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels"

29735556

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"USP8 acts to deubiquitinate SHANK3, which prevents its proteasomal mediated degradation and enhances overall dendritic spine stability."

29735556

USP8 affects SEC31A

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USP8 deubiquitinates SEC31A. 3 / 3

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"We concluded that USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion."

29604273

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"Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A."

29604273

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ubibrowser

"Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion"

29604273

USP8 affects RNF128

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USP8 deubiquitinates RNF128. 2 / 2

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"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."

24917867

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"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."

18535581

Ubiquitinated USP8 deubiquitinates RNF128. 1 / 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."

21078124

USP8 affects NTRK2

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USP8 deubiquitinates NTRK2. 3 / 3

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"TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation."

34005517

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"TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation."

33288548

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"TrkB deubiquitination by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation."

33288548

USP8 affects KDR

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USP8 deubiquitinates KDR. 3 / 3

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

26459808

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

30120232

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"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."

26459808

USP8 affects KCNN4

1 | 2

USP8 deubiquitinates KCNN4. 3 / 3

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"Further, we demonstrated that KCa3.1 is initially ubiquitylated following endocytosis and then deubiquitylated by USP8 prior to lysosomal degradation XREF_BIBR."

24632741

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ubibrowser

"Review"

27775833

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"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."

21828287

USP8 affects GRIA

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USP8 deubiquitinates GRIA. 3 / 3

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"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)."

30568574

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"Furthermore, shRNA mediated knockdown of USP8 is sufficient to enhance the basal level of AMPAR ubiquitination in primary neurons."

29123470

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"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)."

29302259

USP8 affects ERBB2

1 | 2

USP8 deubiquitinates ERBB2. 3 / 3

1 | 2

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

23333852

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ubibrowser

"ERBB2 is a target for USP8-mediated deubiquitination"

21044682

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"We recently showed that Usp8 also deubiquitinates ErbB2, albeit to a much lesser extent than EGFR [10]."

22800866

USP8 affects CFLAR

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USP8 deubiquitinates CFLAR. 3 / 3

1 | 2

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ubibrowser

"USP8 directly deubiquitylates and stabilizes FLIPL"

27321185

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"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]."

27203743

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"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 ."

31845722

USP8 affects CBL

| 3

USP8 deubiquitinates CBL-Y1045F. 1 / 1

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"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]"

21044682

USP8 deubiquitinates CBL. 1 / 1

| 1

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"The Cbl binding site mutants of EGFR (Y1045F) and EGFR-ErbB2 (Y1091F) are also deubiquitinated by Usp8 both with and without EGF stimulation (Figs. 7 and 8)."

21044682

USP8 deubiquitinates CBL-Y1091F. 1 / 1

| 1

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21044682

USP8 affects TARDBP

| 2

Mutated USP8 leads to the deubiquitination of TARDBP. 1 / 1

| 1

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"Moreover, wild-type but not active site mutant UBPY reduced ubiquitination of TDP-43 C-terminal fragments and of a nuclear import impaired mutant."

24825905

USP8 leads to the deubiquitination of TARDBP. 1 / 1

| 1

➶

reach

"In D. melanogaster models, the ubiquitin conjugating enzyme UBE2E3 promotes ubiquitination of TDP-43; in contrast, ubiquitin isopeptidase Y (UBPY) decreased TDP-43 ubiquitination."

27693252

USP8 affects SNCA

2 |

USP8 deubiquitinates SNCA. 2 / 2

2 |

➶

ubibrowser

"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"

30126257

➶

ubibrowser

"Another deubiquitinase, USP8, removes K63-linked ubiquitin chains of α-synuclein and prevents its lysosomal degradation."

27444016

USP8 affects MCPH1

1 | 1

USP8 deubiquitinates MCPH1. 2 / 2

1 | 1

➶

ubibrowser

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

25733871

➶

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."

31845722

USP8 affects LEPR

| 2

USP8 deubiquitinates LEPR. 2 / 2

| 2

➶

reach

"USP8 deubiquitinates the leptin receptor and is necessary for leptin mediated synapse formation."

31199479

➶

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."

33483467

USP8 affects 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."

23382078

➶

ubibrowser

"We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway."

23382078

USP8 affects ITCH

1 | 1

USP8 deubiquitinates ITCH. 2 / 2

1 | 1

➶

ubibrowser

"Review"

27775833

➶

reach

27203743

USP8 affects HIF1A

1 | 1

USP8 deubiquitinates HIF1A. 2 / 2

1 | 1

➶

reach

"HIF1alpha deubiquitination by USP8 is essential for ciliogenesis in normoxia."

24378640

➶

ubibrowser

"Review"

28279784

USP8 affects F2RL1

1 | 1

USP8 leads to the deubiquitination of F2RL1. 2 / 2

1 | 1

➶

ubibrowser

"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."

19684015

➶

reach

"USP8 and AMSH mediate deubiquitination of PAR2 and its sorting from endosomes to lysosomes [XREF_BIBR]."

28448471

USP8 affects 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."

16771824

➶

ubibrowser

No evidence text available

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."

23153581

➶

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."

23153581

USP8 affects 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."

20484045

➶

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."

20484045

USP8 affects monoubiquitylated growth factor receptors

| 1

USP8 leads to the deubiquitination of monoubiquitylated growth factor receptors. 1 / 1

| 1

➶

reach

"The role of USP8 in facilitating the passage of EGFR and Met to the lysosome has been supported by the observation that USP8 can deubiquitylate monoubiquitylated growth factor receptors as well as act on both K48- and K63 linked ubiquitin chains in vitro."

16702236

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]."

27802243

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)."

29302259

USP8 affects TRAF6

| 1

USP8 leads to the deubiquitination of TRAF6. 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."

34688043

USP8 affects 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 affects Smoothened

| 1

USP8 deubiquitinates Smoothened. 1 / 1

| 1

➶

reach

"Smoothened, a key component of Hedgehog pathway, is deubiquitinated by USP8 34 and activation of Hedgehog pathway induces ACTH secretion 35."

25675982

USP8 affects SIRT1

| 1

USP8 deubiquitinates SIRT1. 1 / 1

| 1

➶

reach

"USP8 can directly deubiquitinate SIRT1 and inhibit inflammatory reactions and oxidative stress, thus improving cognitive dysfunction in SAE mice."

37438900

USP8 affects SFRP4

1 |

USP8 deubiquitinates SFRP4. 1 / 1

1 |

➶

ubibrowser

"Review"

27775833

USP8 affects SCNN1A

1 |

USP8 deubiquitinates SCNN1A. 1 / 1

1 |

➶

ubibrowser

"USP8 interacted with ENaC, as detected by co-immunoprecipitation, and it deubiquitinated ENaC."

23297398

USP8 affects RTK

| 1

USP8 deubiquitinates RTK. 1 / 1

| 1

➶

reach

"SFN-USP8 complex deubiquitinates RTKs and facilitates recycling of RTKs to the plasma membrane."

34405018

USP8 affects OMM proteins

| 1

USP8 deubiquitinates OMM proteins. 1 / 1

| 1

➶

reach

29934616

USP8 affects NTRK1

1 |

USP8 deubiquitinates NTRK1. 1 / 1

1 |

➶

ubibrowser

"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"

28335430

USP8 affects NFX1

| 1

USP8 deubiquitinates NFX1. 1 / 1

| 1

➶

reach

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

33417828

USP8 affects MET

1 |

USP8 deubiquitinates MET. 1 / 1

1 |

➶

ubibrowser

"Review"

27919796

USP8 affects MAP3K7

| 1

USP8 leads to the deubiquitination of MAP3K7. 1 / 1

| 1

➶

reach

"USP8 promoted the ubiquitination and the degradation of TAK1."

34839365

USP8 affects KIF23

1 |

USP8 deubiquitinates KIF23. 1 / 1

1 |

➶

ubibrowser

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]."

26683461

USP8 affects GRIA1

1 |

USP8 deubiquitinates GRIA1. 1 / 1

1 |

➶

ubibrowser

"Synaptic Strength Is Bidirectionally Controlled by Opposing Activity-Dependent Regulation of Nedd4-1 and USP8"

25505317

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)."

34414184

USP8 affects FZD8

1 |

USP8 deubiquitinates FZD8 on lysine. 1 / 1

1 |

➶

biopax:reactome

No evidence text available

USP8 affects FZD6

1 |

USP8 deubiquitinates FZD6 on lysine. 1 / 1

1 |

➶

biopax:reactome

No evidence text available

USP8 affects FZD5

1 |

USP8 deubiquitinates FZD5 on lysine. 1 / 1

1 |

➶

biopax:reactome

No evidence text available

USP8 affects FZD4

1 |

USP8 deubiquitinates FZD4 on lysine. 1 / 1

1 |

➶

biopax:reactome

No evidence text available

USP8 affects FZD

| 1

USP8 deubiquitinates FZD. 1 / 1

| 1

➶

reach

"In contrast, Fzd receptors are deubiquitinated by UBPY and ubiquitin specific protease 6 and 8 (USP6 and USP8)."

34414184

USP8 affects FLIP

| 1

USP8 deubiquitinates FLIP. 1 / 1

| 1

➶

reach

"USP8 directly deubiquitylates and stabilizes FLIP L, but not the short isoform."

27321185

USP8 affects ESCRT-associated receptors

| 1

USP8 leads to the deubiquitination of ESCRT-associated receptors. 1 / 1

| 1

➶

reach

"USP8 and UBPY mediated deubiquitination of some ESCRT associated receptors can facilitate their recycling, and USP8 also regulates endocytic sorting by stabilizing ESCRT-0 proteins HGS, STAM, and STAM2."

31705877

USP8 affects ERVK-18

| 1

USP8 deubiquitinates ERVK-18. 1 / 1

| 1

➶

reach

"Furthermore we demonstrated that both EGFR and EGFR-ErbB2 TM are deubiquitinated by the deubiquitination enzyme Usp8, although deubiquitination of ErbB2 was less efficient than that of EGFR [10]."

22800866

USP8 affects ERBB3

1 |

USP8 deubiquitinates ERBB3. 1 / 1

1 |

➶

ubibrowser

"USP8 regulates another EGFR family member, ErbB3 by modulating Nrdp1 (neuregulin-receptor-degradation protein-1)"

25121098

USP8 affects EGFR-ErbB2

| 1

USP8 deubiquitinates EGFR-ErbB2-Y1091F. 1 / 1

| 1

➶

reach

"The Cbl binding site mutants of EGFR (Y1045F) and EGFR-ErbB2 (Y1091F) are also deubiquitinated by Usp8 both with and without EGF stimulation (Figs. 7 and 8)."

21044682

USP8 affects EGF

| 1

USP8 deubiquitinates EGF. 1 / 1

| 1

➶

reach

17720156

USP8 affects CFTR

| 1

USP8 deubiquitinates CFTR. 1 / 1

| 1

➶

reach

"For example, in this and a previous study we observed that neither USP34, nor USP8 deubiquitinate CFTR, and only USP10 activity was inhibited by Cif XREF_BIBR, XREF_BIBR."

21455491

USP8 affects CASP8

| 1

USP8 deubiquitinates CASP8. 1 / 1

| 1

➶

reach

"Our data are consistent with the recent findings that USP8 directly deubiquitylates and stabilizes the long isoform of FLICE like inhibitory protein (FLIP L) in cervical cancer cell line ME-180, which was derived from the metastatic site of epidermoid carcinoma."

30010158