IndraLab

Statements

USP4 affects MAP3K7
1 | 17
USP4 deubiquitinates MAP3K7. 10 / 14
1 | 13
reach
"USP4 deubiquitinates TAK1 in vivo and in vitro."
21331078
reach
"85 The deubiquitinating enzyme ubiquitin‐specific protease 4 (USP4) attenuates major hypertrophic signalling pathways, such as TAK1‐JNK and TAK1‐p38, by removing the K63‐linked polyubiquitination of TAK1."
30102008
ubibrowser
"Using a functional genomic approach, we have identified ubiquitin-specific peptidase 4 (USP4) as a deubiquitinase for TAK1."
21331078
reach
"In addition, USP4 inhibits TNF-alpha-induced activation of NF-kappaB through USP4 deubiquitination of TAK1 XREF_BIBR."
26240016
reach
"Although it has been reported that USP4 deubiquitinates TAK1 and negatively regulates TNF- and IL-1-induced activation of NF-kappaB, how TAK1 ubiquitination is regulated in adaptive immune cells such as T cells and whether such a regulation regulates T cell mediated immune response remain unknown."
23825189
reach
"In view of the data presented here and previous reports, we propose a working model (XREF_FIG), in which that TNFalpha rapidly induces Lys63 linked TAK1 polyubiquitnation and binding of USP4 to TAK1, Lys63 linked TAK1 would be rapidly deubiquitinated by USP4 to attenuate the magnitude of TNFalpha induced Lys63 linked TAK1 polyubiquitination and TAK1 mediated IKK and NF-kappaB activation."
21331078
reach
"In conclusion, our results provide evidence that TNFalpha induces association of USP4 with TAK1 which leads to TAK1 deubiquitination in the TNFalpha mediated NF-kappaB activation."
21331078
reach
"After TAK1 is activated with Lys63 linked polyubiquitination by Dox, USP4 deubiquitinates TAK1 and inhibits TAK1 mediated signaling."
22981905
reach
"Moreover, p38IP scaffolds the deubiquitinase USP4 to deubiquitinate TAK1 once TAK1 is activated."
32410369
reach
"USP4 deubiquitinates TAK1 in vitro and in vivo."
21331078
Modified USP4 leads to the deubiquitination of MAP3K7. 2 / 2
| 2
reach
"Overexpression of USP4 wild-type, but not deuibiquitinase deficient C311A mutant, inhibits both TNFalpha- and TAK1 and TAB1 co-overexpression-induced TAK1 polyubiquitination and NF-kappaB activation."
21331078
reach
"As shown in XREF_FIG, overexpression of USP4 wild-type but not deubiquitinase deficient C311A mutant abrogated TAK1 and TAB1 co-overexpression-induced TAK1 polyubiquitination."
21331078
USP4 deubiquitinates MAP3K7 on K63. 1 / 1
| 1
reach
"USP4 deubiquitinates TAK1 with Lys63 linked polyubiquitination and inhibits Dox induced NF-kappaB activation."
22981905
USP4-C311A leads to the deubiquitination of MAP3K7. 1 / 1
| 1
reach
"USP4 (C311A) mutation did not inhibit the TAK1 polyubiquitination, and phosphorylation of TAK1, = JNK1/2, and p38 in angiotensin treated myocytes."
30186311
USP4 affects HDAC2
1 | 12
USP4 deubiquitinates HDAC2. 10 / 12
1 | 11
ubibrowser
"USP4 inhibits p53 and NF-kappaB through deubiquitinating and stabilizing HDAC2."
26411366
reach
"Taken together, our results suggested that TRPS1 stabilized HDAC2 by functioning as a scaffold protein to bring UPS4 and HDAC2 together forming the TRPS1-UPS4-HDAC2 complex to enhance USP4-directed HDAC2 de-ubiquitination."
30071870
reach
"Another DUB, USP4 deubiquitinates HDAC2 (Histone deacetylases 2) that was shown to interact with p53 thereby inhibiting the level of acetylated p53."
29479529
reach
"XREF_BIBR, XREF_BIBR Of note, our studies show that USP4 deubiquitinates and stabilizes HDAC2 and the expression of USP4 correlates with that of HDAC2 in cancer tissues (XREF_FIG)."
26411366
reach
"Although USP4 alone could reduce HDAC2 ubiquitination level, additional overexpression of TRPS1 significantly enhanced the reduction of HDAC2 ubiquitination (Fig. 3l)."
30071870
reach
"As we demonstrated that USP4 deubiquitinates HDAC2, it is possible that USP4 can stabilize HDAC2."
26411366
reach
"Nonetheless, USP4 might deubiquitinate and stabilize both ARF-BP1 and its substrate HDAC2."
26411366
reach
"However, the mechanism by which USP4 mediates HDAC2 de-ubiquitination contributing to cancer remains unclear.In this study, we show that the TRPS1-USP4-HDAC2 regulatory axis is involved in tumor cell proliferation."
30071870
reach
"Significantly, our results revealed the scaffolding function of TPRS1 in USP4-directed HDAC2 de-ubiquitination and provided new mechanistic insights into the crosstalk between TRPS1, ubiquitin, and histone modification systems leading to tumor growth."
30071870
reach
"Furthermore, our results identified the novel non-transcription factor scaffolding function of the GATA family member TRPS1 in USP4-directed HDAC2 de-ubiquitination."
30071870
Modified USP4 leads to the deubiquitination of HDAC2. 1 / 1
| 1
reach
"As shown in XREF_FIG, overexpression of USP4-WT but not C311A mutant abrogated HDAC2 polyubiquitination."
26411366
USP4 affects TGFBR1
1 | 11
USP4 deubiquitinates TGFBR1. 10 / 12
1 | 11
reach
"USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-beta type I receptor [XREF_BIBR]."
24997798
reach
"This phosphorylation promotes USP4 localization in membrane and cytoplasm, where USP4 deubiquitylates TbetaRI."
24756567
reach
"For instance, USP4 directly interacts with and deubiquitinates TGF-beta type I receptor (TbetaRI), thereby determining the levels of TGF-beta signaling."
27430936
reach
"Mechanistically, we revealed that USP4 interacted directly with and deubiquitinated TGF-beta receptor type I (TGFR-1) to activate the TGF-beta signaling pathway, and subsequently induced the Epithelial-Mesenchymal Transition (EMT) in HCC cells."
30335615
ubibrowser
"USP4 is a DUB for TGF-β type I receptor"
24756567
reach
"USP4 is regulated by AKT phos phorylation and directly deubiquitylates TGF-beta type I receptor."
24027432
reach
"As mentioned above, USP4 binds to and deubiquitinates the TGF-beta type I receptor and associates with AKT, leading to enhanced TGF-beta signalling and AKT induced breast cancer cell migration (Zhang [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27155333
reach
"USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-beta type I receptor."
22706160
reach
"USP4 directly interacts with and deubiquitinates TGF-beta type I receptor (TbetaRI), regulating TGF-beta signaling by controlling TbetaRI levels at the plasma membrane."
28791349
reach
"USP4 can also deubiquitinate TGF-beta type I receptor (TbetaRI) and sustain its plasma membrane expression in a SMAD7 independent fashion, leading to hyperactivation of the TGF-beta pathway."
33681193
USP4 affects PRPF3
1 | 10
USP4 deubiquitinates PRPF3. 10 / 11
1 | 10
reach
"In particular, non proteolytic ubiquitylation of the U4/U6 protein Prp3, promoted by the Prp19 complex, is required for stabilization of the U4/U6 * U5 tri-snRNP, while de-ubiquitylation of Prp3 by Usp4 and Sart3 is required for U4 dissociation and recycling."
28379520
reach
"Moreover, we found that USP15 and USP4 deubiquitinated substrates PRP31 and PRP3 simultaneously."
28088760
reach
"Prp3 is deubiquitinated by Usp4, and is therefore unlikely to be a target for Bre5-Ubp3."
29027900
reach
"Moreover, it was reported that Sart3, Usp4 and Usp15 form a complex in order to de-ubiquitinate Prp3 and Prp31 simultaneously."
| PMC
reach
"The result shows that USP4 no longer deubiquitinates Prp3 in the presence of SART3 DeltaNLS."
27060135
reach
"Deubiquitination of PRP31 and PRP3 by the USP15, SART3, and USP4 complex decreases the affinity towards PRP8 and this regulation is important for the proper splicing of chromosome segregation related genes such as Bub1 and alpha-tubulin."
28088760
reach
"On the other hand, Usp4 and Sart3 promote de-ubiquitination and recycling of Prp3, and this modification weakens its interaction with Prp8 and allows for the dissociation of U4 during activation of the spliceosome [49]."
| PMC
reach
"U5 tri-snRNP has joined the spliceosome, Usp4 deubiquitinates Prp3, decreasing its affinity for Prp8."
24530854
reach
"Prp3 is deubiquitinated by Usp4 and its substrate targeting factor, the U4/U6 recycling protein Sart3, which likely facilitates ejection of U4 proteins from the spliceosome during maturation of its active site."
20595234
ubibrowser
"USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3"
28088760
USP4 affects HUWE1
1 | 10
USP4 deubiquitinates HUWE1. 10 / 11
1 | 10
reach
"USP4 also interacts directly with and deubiquitinates ARF-BP1, leading to the stabilization of ARF-BP1 and subsequent reduction of p53 levels."
28791349
reach
"For example, USP4 interacts directly with and deubiquitinates ARF binding protein 1 (ARF-BP1), leading to the stabilization of ARF-BP1 and subsequent reduction of p53 levels."
26411366
reach
"Furthermore, USP4 interacts directly with and deubiquitinates ARF-BP1, leading to the stabilization of ARF-BP1 and subsequent reduction of p53 levels [XREF_BIBR]."
25972356
reach
"USP4 interacts directly with and deubiquitinates ADP-ribosylatibon factor binding protein 1 (ARFBP1), which results in the stabilization of ARF-BP1 and the subsequent reduction of p53 levels."
27430936
reach
"USP2 deubiquitinates both MDM2 and MDMX [XREF_BIBR, XREF_BIBR] whereas USP4 deubiquitinates ARF-BP1 [XREF_BIBR], another ubiquitin ligase for p53, thus indirectly destabilizing p53 and inhibiting its function."
28035068
reach
"Recently, ARF-BP1 was reported to specifically target HDAC2 for ubiquitination and degradation and USP4 deubiquitinates and stabilizes ARF-BP1."
26411366
reach
"USP4 interacts directly with and deubiquitinates ARF-BP1, leading to the stabilization of ARF-BP1 and subsequent reduction of p53 levels."
21522127
reach
"USP4 has been recently described as a key regulator of p53 stability: USP4 interacts directly and deubiquitylates the E3 HUWE1 (ARF-BP1; MULE), resulting in reduced p53 levels [86]."
23712866
ubibrowser
"USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1."
21522127
reach
"USP4 is a deubiquitinating enzyme which may inhibit p53 by deubiquitinating an important p53 ubiquitin ligase ARF-BP1 [35]."
31987030
USP4 affects TRAF6
1 1 | 7
USP4 deubiquitinates TRAF6. 8 / 8
1 | 7
reach
"Interestingly, USP4 deubiquitinates not only TRAF2 but also TRAF6 and leads to the regulation of cell migration [12]."
| PMC
reach
"Taken together, these findings suggest that USP4 decreases the polyubiquitination of TRAF6 in a ubiquitin specific domain dependent manner."
30194441
reach
"These findings suggest that USP4 deubiquitinates TRAF6 largely in a noncatalytic manner."
30194441
reach
"However, there is no evidence of how USP4 deubiquitinates TRAF6 and TRAF2 proteins; our results prove that USP4 targets TRAF6 for K48 linked deubiquitination."
30194441
reach
"USP4 interacts with and deubiquitinates TRAF6, thereby preventing the activation of NF-kappaB and AP-1 transcription factors and subsequent immune responses."
33511009
reach
"USP4 deubiquitinates TRAF2 and TRAF6, but not TRAF3, and it also rescues IkappaBalpha from degradation in TNFalpha induced HEK cells [XREF_BIBR]."
33138315
reach
"USP4 deubiquitinates TRAF6 and thereby prevents the activation of NF-kappaB and AP-1 transcription factors and subsequent proinflammatory responses."
22262844
ubibrowser
"The downregulation of USP4 expression may promote microglial activation and subsequent neuronal inflammation through NF-κB by attenuating the deubiquitination of TRAF6."
28755289
USP4 deubiquitinates TRAF6 on lysine. 1 / 1
1 |
biopax:reactome
No evidence text available
USP4 affects TRAF2
1 1 | 3
USP4 deubiquitinates TRAF2. 4 / 4
1 | 3
ubibrowser
"Ubiquitin-specific protease 4 (USP4) targets TRAF2 and TRAF6 for deubiquitination and inhibits TNFα-induced cancer cell migration"
22029577
reach
"However, there is no evidence of how USP4 deubiquitinates TRAF6 and TRAF2 proteins; our results prove that USP4 targets TRAF6 for K48 linked deubiquitination."
30194441
reach
"Interestingly, USP4 deubiquitinates not only TRAF2 but also TRAF6 and leads to the regulation of cell migration [12]."
| PMC
reach
"USP4 deubiquitinates TRAF2 and TRAF6, but not TRAF3, and it also rescues IkappaBalpha from degradation in TNFalpha induced HEK cells [XREF_BIBR]."
33138315
USP4 deubiquitinates TRAF2 on lysine. 1 / 1
1 |
biopax:reactome
No evidence text available
USP4 affects PRPF31
1 | 4
USP4 deubiquitinates PRPF31. 5 / 5
1 | 4
reach
"Moreover, it was reported that Sart3, Usp4 and Usp15 form a complex in order to de-ubiquitinate Prp3 and Prp31 simultaneously."
| PMC
reach
"Deubiquitination of PRP31 and PRP3 by the USP15, SART3, and USP4 complex decreases the affinity towards PRP8 and this regulation is important for the proper splicing of chromosome segregation related genes such as Bub1 and alpha-tubulin."
28088760
reach
"When PRP31 was ubiquitinated by PRP19, PRP31 was deubiquitinated by USP4."
28088760
reach
"Moreover, we found that USP15 and USP4 deubiquitinated substrates PRP31 and PRP3 simultaneously."
28088760
ubibrowser
"USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3"
28088760
USP4 affects IRF4
1 | 4
USP4 deubiquitinates IRF4. 5 / 5
1 | 4
ubibrowser
"Review"
28791349
reach
"USP4 deubiquitinates IRF4."
28791349
reach
"To conclude, this study indicated that USP4 interacts with and deubiquitinates IRF4, and also stabilizes IRF4 protein and promotes IRF4 function to facilitate IL-4 expression in Th2 cells, which may be associated with the pathological process of RHD."
28791349
reach
"On the whole, our data indicate that USP4 interacts with and deubiquitinates IRF4, and also stabilizes IRF4 protein and promotes IRF4 function to facilitate IL-4 expression in Th2 cells, which may be related to the pathological process of RHD."
28791349
reach
"Here, we speculated that USP4 may deubiquitinate IRF4, and affect Th2 cell function and may be associated with the pathogenesis of RHD."
28791349
USP4 affects DDX58
1 | 4
USP4 deubiquitinates DDX58. 4 / 4
1 | 3
reach
"Conversely, USP15 and USP4 deubiquitinate TRIM25 and RIG-I, respectively, to stabilize the proteins."
25644461
reach
"RIG-I can be ubiquitinated and degraded by RNF125 (Ring Finger Protein 125) and deubiquitinated and stabilized by USP4."
26454188
ubibrowser
"Furthermore, USP4 was found to interact with RIG-I and remove K48-linked polyubiquitination chains from RIG-I."
23388719
reach
"USP4 deubiquitinates and stabilizes RIG-I to promote type I IFN induction after viral infection [83]."
25651846
USP4 deubiquitinates DDX58 on K48. 1 / 1
| 1
reach
"USP4, it positively regulates the RIG-I-mediated antiviral response by deubiquitinating K48-linked ubiquitin chains and stabilizing RIG-I (77)."
34707613
USP4 affects CTNNB1
1 | 4
USP4 deubiquitinates CTNNB1. 5 / 5
1 | 4
reach
"In a colon cancer cell line, USP4 deubiquitinates beta-catenin and mediates its nuclear transportation, thus promoting Wnt and beta-catenin signaling and cancer cells growth, migration, and invasion."
29080116
reach
"We showed that USP4 deubiquitinates beta-catenin."
26189775
reach
"Ubiquitin-specific protease 4 (USP4) is highly overexpressed in colon cancer and acts as a potent protooncogenic protein by deubiquitinating β-catenin."
37039823
reach
"Deubiquitination of beta-catenin by USP4 reverses the ubiquitination mediated degradation of beta-catenin, upregulating Wnt signalling."
28923280
ubibrowser
"Additionally, DUBs USP14, USP15, USP47, and Fam/USP9X have been reported to prevent β-catenin turnover by inhibiting its Ub-proteasomal degradation"
29080116
USP4 affects TGFB
| 4
USP4 deubiquitinates TGFB. 4 / 4
| 4
reach
"In the cytosol, USP4 deubiquitinates the member of many vital cell signaling pathways, e.g., NF-κB [77], TGF-β [54], Wnt/β-catenin [78], and p53 [79] as well as adenosine A2A receptor [80] and the E3 ligase TRIM21 [81]."
32512887
reach
"USP4 has been reported to enhance TGFbeta signalling by directly interacting with and deubiquitylating type I TGFbeta receptor, ALK5 XREF_BIBR."
25007997
reach
"Mechanistically, hepatocyte USP4 directly bound to and deubiquitinated transforming growth factor-beta activated kinase 1 (TAK1), leading to a suppression of the activation of downstream NF-kappaB and JNK cascades, which in turn reversed the disruption of the IRS-AKT-GSK3beta signaling."
29573006
reach
"The authors further go on to show that USP4 was able to deubiquitylate the TGF-beta receptor I (TbetaRI) directly and rescue it from proteasome mediated degradation."
28425962
USP4 affects PTP4A3
1 | 1 2
USP4 deubiquitinates PTP4A3. 4 / 4
1 | 1 2
ubibrowser
"Review"
28279784
trips
"Mechanistically, we observed that USP4 interacted with and stabilized PRL-3 via deubiquitination."
26669864
reach
"Specifically, up-regulated USP4 potentiated the growth and invasion of colorectal cancer though deubiquitination and stabilization of PRL-3.19 In addition, USP4 transduced Akt activation to TGF-beta signalling by deubiquitinating and stabilizing TGF-beta type I receptor, thus augmented breast cancer cell invasion and migration.33 These studies demonstrate USP4 as a powerful tumour promoter and an important determinant for canonical oncogenic signalling."
29542252
reach
"Deubiquitinating PRL-3 by USP4 leads to AKT activation and E-cadherin reduction in colorectal cancer, where an elevated level of USP4 is associated with tumor size, differentiation, distant metastasis, and poor survival."
33681193
USP4 affects adenosine
| 3
USP4 deubiquitinates adenosine on A2. 2 / 2
| 2
reach
"In contrast to these observations, the deubiquitination of the adenosine A 2A receptor (A 2A R) by USP4 is necessary for the cell surface delivery of a functionally active receptor (XREF_FIG, pathway 4) [XREF_BIBR]."
28448471
reach
"The Adenosine A2 receptor is deubiquitinated by USP4; the ubiquitination status and trafficking of the EGFR growth factor receptor is regulated by the USP8 and STAM complex; the beta2-AR undergoes increased agonist stimulated ubiquitination, lysosomal trafficking, and degradation after knockdown of USPs 20 and 33."
21898592
USP4 deubiquitinates adenosine-A2A. 1 / 1
| 1
reach
"In the cytosol, USP4 deubiquitinates the member of many vital cell signaling pathways, e.g., NF-κB [77], TGF-β [54], Wnt/β-catenin [78], and p53 [79] as well as adenosine A2A receptor [80] and the E3 ligase TRIM21 [81]."
32512887
USP4 affects TRIM21
1 | 2
USP4 deubiquitinates TRIM21. 3 / 3
1 | 2
reach
"In the cytosol, USP4 deubiquitinates the member of many vital cell signaling pathways, e.g., NF-κB [77], TGF-β [54], Wnt/β-catenin [78], and p53 [79] as well as adenosine A2A receptor [80] and the E3 ligase TRIM21 [81]."
32512887
reach
"Oncogenic protein UnpEL and Usp4 deubiquitinates Ro52 by its isopeptidase activity."
16316627
ubibrowser
"Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity"
16316627
USP4 affects TP53
1 | 2
USP4 deubiquitinates TP53. 3 / 3
1 | 2
reach
"USP4 is a deubiquitinating enzyme which may inhibit p53 by deubiquitinating an important p53 ubiquitin ligase ARF-BP1 [35]."
31987030
ubibrowser
"Regulation of p53 is also subject to other DUBs, such as USP4, USP10, USP29, and USP42 [171]."
25121098
reach
"In the cytosol, USP4 deubiquitinates the member of many vital cell signaling pathways, e.g., NF-κB [77], TGF-β [54], Wnt/β-catenin [78], and p53 [79] as well as adenosine A2A receptor [80] and the E3 ligase TRIM21 [81]."
32512887
USP4 affects TCF4
1 | 2
USP4 deubiquitinates TCF4. 3 / 3
1 | 2
ubibrowser
"DUBs regulate canonical Wnt signaling, by modulating?β-catenin activity. USP4 deubiquitinases TCF4, to suppress?β-catenin dependent transcription"
25121098
reach
"For example, USP4 interacts with and deubiquitinates TCF4, which inhibits beta-catenin-dependent transcription [XREF_BIBR]."
33051403
reach
"USP4 deubiquitinated a subpopulation of TCF4."
28923280
USP4 affects SMAD4
1 | 2
USP4 leads to the deubiquitination of SMAD4. 3 / 3
1 | 2
reach
"Interestingly, these speculations have been confirmed that HECW1 can promote the proliferation, migration and invasion of cancer cells by inducing the ubiquitination and degradation of SMAD4 (34), while USP4 can mediate the deubiquitination of SMAD4, leading to the expression of apoptotic proteins (35) ."
34669962
ubibrowser
"We demonstrated that ubiquitin-specific protease (USP) 4 strongly induces activin/BMP signaling by removing the inhibitory monoubiquitination from SMAD4."
28468752
reach
"USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling."
28468752
USP4 affects PDPK1
1 | 2
USP4 deubiquitinates PDPK1. 3 / 3
1 | 2
reach
"USP4 deubiquitinates PDK1 and co-localizes at the plasma membrane."
22347420
reach
"In addition, the closely related USP15, which shares 61% amino acid sequence identity with USP4 XREF_BIBR, had no effect on Ub-PDK1 levels, further suggesting that the ability of USP4 to deubiquitinate PDK1 is specific."
22347420
ubibrowser
"By screening a library of ubiquitin proteases, we further identify the Ubiquitin-Specific Protease 4 (USP4) as an enzyme that removes ubiquitin from PDK1 in vivo and in vitro and co-localizes with PDK1 at the plasma membrane when the two proteins are overexpressed, indicating direct deubiquitination."
22347420
USP4 affects HAS2
1 | 2
USP4 deubiquitinates HAS2. 3 / 3
1 | 2
reach
"For example, USP4 targets and deubiquitinates hyaluronan synthase 2 (HAS2), but USP4 does not maintain the stability of HAS, and, rather, loss of USP4 increases hyaluronan synthesis [33]."
| PMC
reach
"The de-ubiquitinase USP17 preferentially deconjugated polyubiquitin chains from HAS2, whereas USP4 significantly reduced the monoubiquitination of HAS2; thus, the two DUBs were found to selectively affect the activity and stability of HAS2."
28604766
ubibrowser
"USP17 efficiently removed polyubiquitination, whereas USP4 preferentially removed monoubiquitination of 6myc-HAS2.;The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2 and differentially affect its function;USP17 and USP4 differently affect HAS2 ubiquitination, and the stability and function of HAS2"
28604766
USP4 affects E3_Ub_ligase
| 3
USP4 deubiquitinates E3_Ub_ligase. 3 / 3
| 3
reach
"In contrast to USP2a, USP4 deubiquitinates and stabilizes a different E3 that ubiquitinates p53 called ARF-BP1, thereby destabilizing p53 [XREF_BIBR]."
23151129
reach
"In the cytosol, USP4 deubiquitinates the member of many vital cell signaling pathways, e.g., NF-κB [77], TGF-β [54], Wnt/β-catenin [78], and p53 [79] as well as adenosine A2A receptor [80] and the E3 ligase TRIM21 [81]."
32512887
reach
"USP4 interacts with and deubiquitylates another E3 ubiquitin ligase for p53, ARF-BP1/Mule/HUWE, leading to the stabilization of ARF-BP1 and subsequent reduction of p53 levels."
27516771
USP4 affects insulin receptors
| 2
USP4 deubiquitinates insulin receptors. 2 / 2
| 2
reach
"Upregulation of USP4 reduces the ubiquitination and degradation of insulin receptors, upregulates the level of insulin receptors, and ultimately improves insulin resistance."
34603025
reach
"USP4 is a deubiquitinating enzyme and may deubiquitinate insulin receptors to inhibit their degradation, which maintains the expression level of insulin receptors on the membrane surface and improves insulin resistance."
34603025
USP4 affects RIPK1
1 1 |
USP4 deubiquitinates RIPK1. 1 / 1
1 |
ubibrowser
"USP4 directly interacts with receptor-interacting protein 1 (RIP1) and deubiquitinates K63-linked ubiquitination from RIP1."
23313255
USP4 deubiquitinates RIPK1 on K377. 1 / 1
1 |
biopax:reactome
No evidence text available
USP4 affects INS
| 2
USP4 deubiquitinates INS. 2 / 2
| 2
reach
"USP4 is a deubiquitinating enzyme and may deubiquitinate insulin receptors to inhibit their degradation, which maintains the expression level of insulin receptors on the membrane surface and improves insulin resistance."
34603025
reach
"Upregulation of USP4 reduces the ubiquitination and degradation of insulin receptors, upregulates the level of insulin receptors, and ultimately improves insulin resistance."
34603025
USP4 affects AQP2
| 2
Modified USP4 leads to the deubiquitination of AQP2. 1 / 1
| 1
reach
"Taken together, the data suggest that USP4 is a key regulator of AQP2 deubiquitylation and that loss of USP4 leads to increased AQP2 ubiquitylation, decreased AQP2 levels, and decreased cell surface AQP2 accumulation upon VP treatment."
30901874
USP4 deubiquitinates AQP2. 1 / 1
| 1
reach
"AQP2 and USP4 co-immunoprecipitated from mpkCCD14 cells and mouse kidney, and in vitro, USP4 can deubiquitylate AQP2."
30901874
USP4 deubiquitinates signaling receptor activity on A2. 1 / 1
| 1
reach
"USP4 has been shown to deubiquitinate A 2a receptor, a G S -coupled receptor at the cell surface, and deubiquitination of A 2a receptor by USP4 enhanced cell surface expression of the receptor in cult[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25078763
USP4 affects polyubiquitin chain
| 1
USP4 deubiquitinates polyubiquitin chain. 1 / 1
| 1
reach
"A study demonstrates that USP4 inhibits this pathway by deubiquitinating the polyubiquitin chain from Dvl, resulting in inhibiting of Wnt signal and decreased osteoblast differentiation and mineralization [70]."
30123285
USP4 affects p38
| 1
USP4-C311A leads to the deubiquitination of p38. 1 / 1
| 1
reach
"USP4 (C311A) mutation did not inhibit the TAK1 polyubiquitination, and phosphorylation of TAK1, = JNK1/2, and p38 in angiotensin treated myocytes."
30186311
USP4 affects Wnt/β-catenin
| 1
USP4 deubiquitinates Wnt/β-catenin. 1 / 1
| 1
reach
"In the cytosol, USP4 deubiquitinates the member of many vital cell signaling pathways, e.g., NF-κB [77], TGF-β [54], Wnt/β-catenin [78], and p53 [79] as well as adenosine A2A receptor [80] and the E3 ligase TRIM21 [81]."
32512887
USP4 affects Wnt
| 1
USP4 deubiquitinates Wnt. 1 / 1
| 1
reach
"USP4 also deubiquitinates other Wnt signaling components such as Nik and TCF4 [81]."
30123285
USP4 affects USP4
1 |
USP4 deubiquitinates USP4. 1 / 1
1 |
ubibrowser
"UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself"
16472766
USP4 affects TRIM25
| 1
USP4 deubiquitinates TRIM25. 1 / 1
| 1
reach
"Conversely, USP15 and USP4 deubiquitinate TRIM25 and RIG-I, respectively, to stabilize the proteins."
25644461
USP4 affects TRAF3
| 1
USP4 deubiquitinates TRAF3. 1 / 1
| 1
reach
"USP4 deubiquitinates TRAF2 and TRAF6, but not TRAF3, and it also rescues IkappaBalpha from degradation in TNFalpha induced HEK cells [XREF_BIBR]."
33138315
USP4 affects TGFbeta receptor
| 1
USP4 leads to the deubiquitination of TGFbeta receptor. 1 / 1
| 1
reach
"USP4 has been reported to enhance TGFbeta signalling by directly interacting with and deubiquitylating type I TGFbeta receptor, ALK5 XREF_BIBR."
25007997
USP4 affects TGFBR
| 1
USP4 deubiquitinates TGFBR. 1 / 1
| 1
reach
"The authors further go on to show that USP4 was able to deubiquitylate the TGF-beta receptor I (TbetaRI) directly and rescue it from proteasome mediated degradation."
28425962
USP4 affects SRSF1
| 1
USP4 deubiquitinates SRSF1. 1 / 1
| 1
reach
"As shown in Supplementary Fig. 3A, B, SRSF1 was not deubiquitinated by USP15 or USP4, respectively."
35027535
USP4 affects RORgammat
| 1
USP4 deubiquitinates RORgammat. 1 / 1
| 1
reach
"Interestingly, TGF-beta plus IL-6 enhanced USP4 mediated deubiquitination of RORgammat."
25821221
USP4 affects RORC
1 |
USP4 deubiquitinates RORC. 1 / 1
1 |
ubibrowser
"Ubiquitin-specific protease 4 promotes Th17 cell function under inflammation by deubiquitinating and stabilizing RORγt"
25821221
USP4 affects RNPS1
1 |
USP4 deubiquitinates RNPS1. 1 / 1
1 |
ubibrowser
"Although RNPS1 is polyubiquitinated by both K48- and K63-linkages, USP4 exclusively deubiquitinates K63-linked polyubiquitin chains of RNPS1."
27990632
USP4 affects RHEB
| 1
USP4 leads to the deubiquitination of RHEB. 1 / 1
| 1
reach
"Thus, we propose a mechanistic model whereby Rheb mediated mTORC1 activation is dictated by a dynamic opposing act between Rheb ubiquitination and deubiquitination that are catalyzed by RNF152 and USP4 respectively."
30514904
USP4 affects RBL2
1 |
USP4 deubiquitinates RBL2. 1 / 1
1 |
ubibrowser
"USP4, reported as an oncogenic protein, is known to interact with the pocket proteins (Rb, p107, and p130) although no deubiquitinating activity has been reported"
25121098
USP4 affects RBL1
1 |
USP4 deubiquitinates RBL1. 1 / 1
1 |
ubibrowser
"USP4, reported as an oncogenic protein, is known to interact with the pocket proteins (Rb, p107, and p130) although no deubiquitinating activity has been reported"
25121098
USP4 affects RBBP8
| 1
USP4 deubiquitinates RBBP8. 1 / 1
| 1
reach
"Although USP4 does not directly deubiquitinate CtIP, its interaction with CtIP is essential for HR as blocking their binding reduces HR efficiency."
33681193
USP4 affects RB1
1 |
USP4 deubiquitinates RB1. 1 / 1
1 |
ubibrowser
"USP4, reported as an oncogenic protein, is known to interact with the pocket proteins (Rb, p107, and p130) although no deubiquitinating activity has been reported"
25121098
USP4 affects PPIA
1 |
USP4 deubiquitinates PPIA. 1 / 1
1 |
ubibrowser
"Mechanistically, cyclophilin A (CypA) was identified as an important molecule for USP4-mediated oncogenic activity in HCC."
29396555
USP4 affects PDGFR
| 1
USP4 deubiquitinates PDGFR. 1 / 1
| 1
reach
"By overexpressing a panel of deubiquitinating enzymes (DUBs), we found that USP17 and USP4 efficiently deubiquitinate PDGF receptor β (PDGFRβ) and are able to remove both Lys63 and Lys48-linked polyubiquitin chains from the receptor."
35064336
USP4 affects PDGF
| 1
USP4 deubiquitinates PDGF. 1 / 1
| 1
reach
"By overexpressing a panel of deubiquitinating enzymes (DUBs), we found that USP17 and USP4 efficiently deubiquitinate PDGF receptor β (PDGFRβ) and are able to remove both Lys63 and Lys48-linked polyubiquitin chains from the receptor."
35064336
USP4 affects PDGF receptor
| 1
USP4 deubiquitinates PDGF receptor. 1 / 1
| 1
reach
"By overexpressing a panel of deubiquitinating enzymes (DUBs), we found that USP17 and USP4 efficiently deubiquitinate PDGF receptor β (PDGFRβ) and are able to remove both Lys63 and Lys48-linked polyubiquitin chains from the receptor."
35064336
USP4 affects NR2C2
1 |
USP4 deubiquitinates NR2C2. 1 / 1
1 |
ubibrowser
"Mechanistically, hepatocyte USP4 directly bound to and deubiquitinated transforming growth factor-β activated kinase 1 (TAK1)"
29573006
USP4 affects NFkappaB
| 1
Modified USP4 leads to the deubiquitination of NFkappaB. 1 / 1
| 1
reach
"Overexpression of USP4 wild-type, but not deuibiquitinase deficient C311A mutant, inhibits both TNFalpha- and TAK1 and TAB1 co-overexpression-induced TAK1 polyubiquitination and NF-kappaB activation."
21331078
USP4 affects NFKBIA
| 1
USP4 leads to the deubiquitination of NFKBIA. 1 / 1
| 1
reach
"Therefore, we further analyzed the effect of USP4 knockdown on the TNFalpha induced IKK phosphorylation, IkappaBalpha phosphorylation, ubiquitination and degradation."
21331078
USP4 affects JNK
| 1
USP4-C311A leads to the deubiquitination of JNK. 1 / 1
| 1
reach
"USP4 (C311A) mutation did not inhibit the TAK1 polyubiquitination, and phosphorylation of TAK1, = JNK1/2, and p38 in angiotensin treated myocytes."
30186311
USP4 affects Interferon
| 1
USP4 deubiquitinates Interferon. 1 / 1
| 1
reach
"We speculated that ubiquitin specific peptidase4 (USP4) may deubiquitinate interferon regulatory factor4 (IRF4) and affect Thelper type2 (Th2) cell function."
28791349
USP4 affects IRF8
1 |
USP4 deubiquitinates IRF8. 1 / 1
1 |
ubibrowser
"In the present study, we demonstrate that ubiquitin-specific protease (USP)4 physically interacted with interferon regulatory factor 8 (IRF8) function via a K48-linked deubiquitinase, which stabilized IRF8 protein levels in Treg cells."
28477415
USP4 affects IKK_complex
| 1
USP4 leads to the deubiquitination of IKK_complex. 1 / 1
| 1
reach
"Therefore, we further analyzed the effect of USP4 knockdown on the TNFalpha induced IKK phosphorylation, IkappaBalpha phosphorylation, ubiquitination and degradation."
21331078
USP4 affects Histone
| 1
USP4 deubiquitinates Histone. 1 / 1
| 1
reach
"Another DUB, USP4 deubiquitinates HDAC2 (Histone deacetylases 2) that was shown to interact with p53 thereby inhibiting the level of acetylated p53."
29479529
USP4 affects DVL
| 1
USP4 leads to the deubiquitination of DVL. 1 / 1
| 1
reach
"USP4 was initially identified as a repressor of the Wnt and beta-catenin signaling pathway, given that USP4 can mediate deubiquitination and stabilization of Dvl, a key molecule involved in the turnover of cytosolic beta-catenin."
33681193
USP4 affects BIRC2
| 1
USP4 deubiquitinates BIRC2. 1 / 1
| 1
reach
"In contrast, USP4 wild-type failed to deubiquitinate cIAP1 (XREF_SUPPLEMENTARY)."
21331078
USP4 affects ADP-ribosylatibon factor-binding protein 1
| 1
USP4 deubiquitinates ADP-ribosylatibon factor-binding protein 1. 1 / 1
| 1
reach
"USP4 interacts directly with and deubiquitinates ADP-ribosylatibon factor binding protein 1 (ARFBP1), which results in the stabilization of ARF-BP1 and the subsequent reduction of p53 levels."
27430936
USP4 affects ADORA2A
1 |
USP4 deubiquitinates ADORA2A. 1 / 1
1 |
ubibrowser
No evidence text available