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TP53 binds USP7. 352 / 373
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"These results provide rationale for the use of cabozantinib in treatment of patients with cancers harboring p53-Y220C mutant.We show that USP7, a deubiquitinase type involved in the stabilization and removal of lysine-linked ubiquitin from various substrate proteins, physically interacts with p53 protein (Fig. 4A) and facilitates the deubiquitination and stabilization of p53 protein (Fig. 4D and Fig. S5A), and cabozantinib can inhibit the interaction between USP7 and p53 , resulting in decreased ubiquitination and amount of p53 protein (Fig. 4)."
39793887
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"HAUSP interacted with and deubiquitinated p53, leading to increased p53 levels."
15916963
biogrid
No evidence text available
32807901
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"It has been reported that the EBNA1 protein binds to USP7 with high affinity and impairs the interaction of p53 and USP7."
36624687
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"USP7 binds to and directly deubiquitinates p53 and inhibits its degradation."
36624687
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"Interest in USP7 was renewed by the observation that USP7 binds to the C-terminal domain of p53, promotes its de-ubiquitination and subsequent stabilization [24] ."
17961905
biogrid
No evidence text available
37438558
sparser
"USP7 was also shown to be involved in the stress-induced p53 translocation to the mitochondria since a stress-inducible USP7-p53 complex was formed at the mitochondria resulting in p53 de-ubiquitinati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17961905
biogrid
No evidence text available
17380154
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"The interaction between p53 and USP7 can be disrupted by EBNA1."
33505922
sparser
"It has been reported that the EBNA1 protein binds to USP7 with high affinity and impairs the interaction of p53 and USP7."
36624687
biogrid
No evidence text available
37438558
biogrid
No evidence text available
37438558
sparser
"USP7 binds to and directly deubiquitinates p53 and inhibits its degradation."
36624687
biogrid
No evidence text available
14506283
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"32 In response to DNA damage, HAUSP interacts with p53, causing its stabilization."
25843733
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"However, in cells infected by EBV, EBNA-1 can effectively block the interaction between HAUSP and p53, which results in degradation of the latter, controlled by the ubiquitin-proteasome system."
25843733
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"As depicted in xref D, endogenous HAUSP clearly interacted with endogenous epitope-tagged p53 in HCT116 cells, demonstrating the functional integrity of the epitope-tagged allele of p53 and providing proof-of-principle for the use of cells with endogenous epitope-tagged alleles for the confirmation of endogenous protein–protein interactions."
18784188
biogrid
No evidence text available
34591612
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"To demonstrate the effect of cabozantinib on the interaction between USP7 and p53 , we conducted GST-pulldown and co-immunoprecipitation assays in the cells treated with cabozantinib."
39793887
reach
"Our in vitro–binding assays revealed that cabozantinib directly disrupted the binding between p53 and USP7(Fig. 4E)."
39793887
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"Collectively, these results demonstrate that cabozantinib can disrupt the interaction between USP7 and p53 , inducing the CHIP-mediated degradation through K48-linked ubiquitination."
39793887
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"These data suggest a potential impact of this configuration alteration on binding between p53 and USP7."
39793887
sparser
"Furthermore, USP7 interacts with other p53 regulators, such as the Alternate Reading Frame (ARF), which activates p53 [ xref ]."
41157055
biogrid
No evidence text available
30651545
biogrid
No evidence text available
30651545
biogrid
No evidence text available
16474402
sparser
"USP7 also interacts with the tumor suppressor gene p53 ( xref ) and regulates its stability ( xref )."
34558642
biogrid
No evidence text available
16474402
sparser
"KSHV vIRF4 interacts with USP7 to inhibit p53-mediated antiviral activity [ xref ], whereas EBV EBNA1 disrupts p53-USP7 interaction, to promote their latent establishment [ xref ]."
33670221
biogrid
No evidence text available
16474402
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"To test this model, we designed a TRAF domain mutant based on structural homology to USP7, which binds peptide ligands in p53 (Hu et al., 2006; Sheng et al., 2006)."
39416052
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"Intriguingly, Becker et al. described that the hyperubiquitylation of p53 contributes to its aberrant cytoplasmic retention in neuroblastoma in association with the impaired interaction between p53 and HAUSP which catalyzes the deubiquitylation of p53 [XREF_BIBR]."
21188172
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"The interaction of HAUSP with the C-terminus of p53 [62] in the vicinity of the ubiquitinated lysine residues supports the notion that HAUSP acts directly on p53."
15865930
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No evidence text available
16845383
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No evidence text available
36243803
trips
"Indeed, this mutant p53 protein can be degraded by Mdm2 but fails to interact with HAUSP both in vitro and in vivo."
17525743
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"Immunoprecipitation using an anti-HAUSP antibody was performed to confirm whether the differences in p53 stability between MCF7 and TamR cells were due to differential interactions between HAUSP and p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32987137
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"The findings revealed that interaction between p53 and HAUSP was stronger in MCF7 cells ( Fig. 4 G)."
32987137
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"However, when GCN5 was overexpressed in MCF7 cells, the interaction between p53 and HAUSP decreased to levels similar to those observed in TamR cells."
32987137
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"In comparison, inhibition of AIB1 in GCN5-overexpressing MCF7 cells restored the interaction between p53 and HAUSP to the levels observed in MCF7 cells."
32987137
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"It is shown that the N-terminal domain of USP7 binds two closely spaced 4-residue sites in P53, falling between P53 residues 359–367 [6] ."
22750444
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No evidence text available
22084066
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"As efforts to obtain crystals of the p53 and HAUSP complex were not successful, they generated protein chimeras -- made of half p53 peptides and half HAUSP TRAF like domain -- to determine the complex 's structure and mechanism of binding."
20076526
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"However, in EBV infected cells EBNA-1 can efficiently block the interaction between HAUSP and p53 resulting in ubiquitin-proteasome mediated degradation of p53 ( xref , xref )."
21372216
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"In addition, Mdm2 mediates complex formation between HAUSP and p53 [161] ."
19897040
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"Indeed, the microprotein may either competitively inhibit the interaction of p53 with FBXW7 (a p53 ubiquitin ligase) or promote p53 interaction with USP7 (a p53 deubiquitinase), thus reducing p53 degradation."
41131620
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No evidence text available
21845734
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"17 , 18 Originally, ectopic overexpression studies revealed that USP7 can directly bind to and deubiquitinate p53, leading to its stabilization."
36952348
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"With respect to NPC cells, a decrease in p53 levels in NPC cells that are expressing EBNA-1 compared to non-expressing cells has been observed, suggesting that the interference of EBNA-1 in USP7 interaction with p53 could suppress apoptosis [ xref ]."
35053275
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"Further research reveals that p53 interacts with the deubiquitinase USP7, inducing its nuclear translocation and removing the monoubiquitination of histone H2B at lysine 120 (H2Bub1), thereby reducing the expression of SLC7A11 [ xref ]."
41226699
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"Although the effects of HAUSP on p53, Mdm2, and MdmX presumably occurs in the nucleus, HAUSP localizes to both the nucleus and cytoplasm, and mitochondrial HAUSP has been shown to deubiquitinate a cytoplasmic pool of monoubiquitinated p53 upon arriving at the mitochondria through a stress induced p53 and HAUSP complex, which thereby creates a sub-fraction of non ubiquitinated p53 that can induce transcription independent apoptosis [XREF_BIBR]."
21624367
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"Given that USP7 binds the C-terminal domain of p53 XREF_BIBR and that this domain regulates DNA binding by the p53 core domain, we asked whether USP7 affects the DNA binding activity of p53 and downstream p53 functions."
20885946
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"It was reported that the affinity of USP7-EBNA1 was 10-fold higher than USP7-p53, implying the strong binding of USP7-EBNA1 ( xref )."
31921057
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"To further investigate the relationship between USP7 and apoptotic proteins, the potential interaction between USP7 and p53 was evaluated in H9C2 cells."
35127703
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"Further insight into the mechanism by which ATM switches the interactions between HAUSP, Mdmx, Mdm2 and p53, to favor p53 activation may offer new tools for therapeutic intervention in the p53 pathway for cancer treatment."
16082221
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"USP7 interacts with and deubiquitinates p53, thereby stabilizing and protecting it from Mdm2 mediated degradation [XREF_BIBR]."
18687060
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"Surprisingly, however, we have found that direct interaction between HAUSP and p53 is not absolutely required for it to antagonize efficiently Mdm2-mediated ubiquitination of p53 and that HAUSP is capable of enzymatically functioning in trans on p53 by using Mdm2 as a bridge."
17525743
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"We further show that ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7."
25283148
sparser
"The interaction between p53 and USP7 can be disrupted by EBNA1 ( xref )."
33505922
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"RORalpha promotes interactions between p53 and USP7 but does not affect interactions between p53 and MDM2."
25283148
sparser
"However, the ChIP assay showed that USP7 hardly interacted with p53 in chromatin levels ( xref ), suggesting that USP7 regulated p53 expression in the post-translational stage."
35127703
sparser
"The hyperubiquitylation of p53 in neuroblastoma proposed in this model is not caused by MDM2 (E3 ligase) overexpression and/or herpesvirus-associated ubiquitin-specific protease (HAUSP) (p53-deubiquitylating enzyme) downregulation, but due to an impaired p53-HAUSP interaction [ xref ]."
33007410
sparser
"RORα promotes interactions between p53 and USP7 but does not affect interactions between p53 and MDM2 (ref. xref )."
25283148
sparser
"In this study, we found that USP7 interacts with p53 protein."
35127703
biogrid
No evidence text available
26460617
sparser
"Originally, ectopic overexpression studies showed that USP7 can bind and stabilize p53 through deubiquitylation ( Li et al., 2002 )."
24462112
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"In response to genotoxic stress, USP7 binds and deubiquitylates p53 thereby protecting it from proteasome mediated degradation."
19834552
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"Crystal structure analysis showed that USP7 binds to its substrate p53 and its inhibitory interactor Epstein-Barr nuclear antigen 1 (EBNA1) protein through the same pocket but the former binding partner p53 exhibit weaker contacts with USP7 [XREF_BIBR, XREF_BIBR]."
28031783
sparser
"ABRO1 (also known as FAM175B) also contributes to the p53 response by stabilizing the p53-USP7 interaction and promoting USP7-mediated p53 deubiquitination ( xref )."
32850836
sparser
"The p53-USP7 interaction is also negatively regulated by the TSPYL5 inhibitor protein ( xref )."
32850836
sparser
"TSPYL5 disrupts the p53-USP7 interaction, leading to increased polyubiquitination and degradation of p53."
32850836
sparser
"Meanwhile, our co-IP assays showed that USP7 could directly bind to p53 in each LSCC cell line with or without p53 mutation ( xref C)."
35696794
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"HAUSP (herpesvirus-associated ubiquitin-specific protease) binds to the transcription factor and tumor suppressor p53 (Li et al. 2002)."
35302693
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"Furthermore, PairExplainer can also identify the MATH structural domain mediating the competitive binding of USP7 to p53 and MDM2 (Supplementary Data 7)."
38806474
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"Upon arrival at mitochondria, p53 undergoes rapid deubiquitination by mitochondrial HAUSP via a stress induced mitochondrial p53 and HAUSP complex, which generates the apoptotically active non ubiquitinated p53."
19007744
biogrid
No evidence text available
24462112
biogrid
No evidence text available
24462112
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"The critical residues for the interaction between USP7 and p53 are amino acids 53-208 of the USP7 N-terminal domain and amino acids 357-382 of the p53 regulatory region C-terminal domain XREF_BIBR."
25283148
reach
"Our results indicate that the association between ABRO1, USP7 and p53 occurs at non overlapping regions of the proteins, suggesting that these three components might form a protein complex."
25283148
biogrid
No evidence text available
35831314
sparser
"GRA16 is exported into the host cell nucleus and binds the host Ub hydrolase HAUSP, modulating the cell cycle via HAUSP-dependent p53 regulation[ xref , xref ]."
27870901
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"Further examination using a sequential immunoprecipitation assay confirmed that ABRO1, p53 and USP7 were present in the same complex (XREF_FIG)."
25283148
sparser
"The down-regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53)."
16450335
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"34 This action is functionally similar to that previously reported for the viral protein EBNA1, which competitively inhibits HAUSP and p53 complex formation."
29967688
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"TSPYL5 is a poor prognostic factor for breast cancer and interacts with HAUSP to impair the HAUSP-p53 interaction, suppressing p53 function and resulting in enhanced cell proliferation. xref This action is functionally similar to that previously reported for the viral-protein EBNA1, which competitively inhibits HAUSP-p53 complex formation. xref "
29967688
reach
"Based on the results showing association of ABRO1, p53 and USP7, we presumed that ABRO1 might promote interaction between USP7 and p53, and regulate USP7 dependent deubiquitination of p53."
25283148
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"We therefore examined the effect of ABRO1 on the interaction between USP7 and p53."
25283148
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"As shown in XREF_FIG, ectopic expression of ABRO1 in HCT 116 p53 +/+ cells enhanced the interaction between USP7 and p53, whereas knockdown of ABRO1 weakened the interaction between USP7 and p53 in the presence of MG132 (XREF_FIG)."
25283148
sparser
"Intriguingly, Becker et al. described that the hyperubiquitylation of p53 contributes to its aberrant cytoplasmic retention in neuroblastoma in association with the impaired interaction between p53 and HAUSP which catalyzes the deubiquitylation of p53 [ xref ]."
21188172
reach
"Becker and colleagues argue that impairment of the interaction between the de-ubiquitylating protease USP7 and p53 may be responsible for this accumulation, as the binding sites on p53 for PARC and US[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18203645
sparser
"Therefore, the identification and investigation of proteins interacting with HAUSP is of significance for deeply understanding p53 signal pathways."
31647545
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"The deubiquitinase USP7 binds Mdm2 or p53 via its N-terminal TRAF-domain or C-terminal region in a mutually exclusive manner to remove ubiquitins and stabilize the two proteins [XREF_BIBR - XREF_BIBR]."
26460617
sparser
"The findings revealed that interaction between p53 and HAUSP was stronger in MCF7 cells ( Fig. 4 G)."
32987137
sparser
"However, when GCN5 was overexpressed in MCF7 cells, the interaction between p53 and HAUSP decreased to levels similar to those observed in TamR cells."
32987137
sparser
"In comparison, inhibition of AIB1 in GCN5-overexpressing MCF7 cells restored the interaction between p53 and HAUSP to the levels observed in MCF7 cells."
32987137
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"However, in SAMe-D cells the levels of HAUSP were higher, and there was a functional interaction between p53 and HAUSP."
20815019
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"The N-terminal region of Bat3 containing an ubiquitin-linked domain was found to have capacity to form a stable complex with both HAUSP ( xref , lane 3) and p53 ( xref , lane 3), but other deletions, which are lacking the N-terminus, completely abolish the ability to form complexes ( xref , lanes 4 and 5; xref , lanes 5 and 6)."
31647545
reach
"USP7 can bind directly to Mdm2 or p53 in a mutually exclusive manner."
26460617
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"In addition, USP7 can interact indirectly with p53, using Mdm2 as a bridge, resulting in the formation of USP7-Mdm2-p53 complexes."
26460617
sparser
"So, vIRF-4 can interfere with p53-HAUSP Mdm2 to break the cell cycle pause and apoptosis activation by p53 and all together promote uncontrolled cell proliferation and transformation in host cells. xref The tegument protein ORF-64 of KSHV is a viral cysteine protease with DUB activity that interacts with IFN signaling."
37363356
sparser
"We first showed that Bat3 extended the half-life of p53 and activated p53-dependent transcription and cell growth repression by forming a complex with HAUSP and p53 ( xref , xref xref )."
31647545
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"Interestingly, STIP knock down seem to have a more profound impact on the interaction between USP7 and Mdm2 than the interaction between USP7 and p53."
26460617
sparser
"We have discovered that the Epstein-Barr nuclear antigen 1 protein of Epstein-Barr virus binds with high affinity to USP7 and disrupts the USP7-p53 interaction."
15494000
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"PFKFB3 nuclear translocation improves diabetic retinopathy by attenuating endothelial cell senescence through inhibition of USP7-p53 axis."
41655956
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"Consistent with this, our results reveal that STIP knock down have a more profound impact on the interaction between USP7 and Mdm2 than the interaction between USP7 and p53."
26460617
sparser
"The critical residues for the interaction between USP7 and p53 are amino acids 53–208 of the USP7 N-terminal domain and amino acids 357–382 of the p53 regulatory region C-terminal domain xref ."
25283148
biogrid
No evidence text available
29748603
sparser
"Based on the results showing association of ABRO1, p53 and USP7, we presumed that ABRO1 might promote interaction between USP7 and p53, and regulate USP7-dependent deubiquitination of p53."
25283148
sparser
"Nuclear-localized PFKFB3 interacted with USP7, a critical modulator of the p53 pathway, and regulated the USP7-p53 axis by constraining their coupling, thereby promoting proteasomal degradation of p53."
41655956
sparser
"USP7 also interacts with the polyubiquitinated p53 and promotes p53 deubiquitination and stability ( xref )."
20531303
sparser
"Our findings highlighted the essential role of nuclear PFKFB3 dysfunction and USP7-p53 axis dysregulation in mediating EC senescence under diabetic stress, suggesting that targeting PFKFB3 nuclear translocation may be a novel therapeutic strategy for the prevention of diabetic retinopathy."
41655956
sparser
"As demonstrated with the USP7-MDM2 axis, selective inhibition using HBX 41108 inhibits MDM2 deubiquitination without affecting the USP7-p53 axis, resulting in selective p53 stabilization and MDM2 degradation [ xref ]."
40835840
sparser
"In contrast, USP7-p53 interaction was not affected when control siRNA was transfected."
25283148
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"Moreover, the interaction between p53 and USP7 was enhanced when SNORD50A/B was deleted while decreased when SNORD50A/B was ectopically expressed (Supplementary Fig. S12)."
33742136
sparser
"We therefore examined the effect of ABRO1 on the interaction between USP7 and p53."
25283148
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"The interaction of EBNA1 with the N-terminal USP domain appears 10-fold higher in affinity than the interaction of USP7 with p53, which would suggest that EBNA1 may interfere with p53 binding to USP7 and thus promote cell cycle progression and prevent apoptosis."
15359630
sparser
"As shown in xref , ectopic expression of ABRO1 in HCT 116 p53 +/+ cells enhanced the interaction between USP7 and p53, whereas knockdown of ABRO1 weakened the interaction between USP7 and p53 in the presence of MG132 ( xref )."
25283148
sparser
"The cytoplasmic accumulation of HAUSP allows HAUSP-p53 interaction and leads to a more steady cytoplasmic p53 form, thus, controlling the apoptotic response through this molecule [ xref ]."
33513829
reach
"We next verified that HAUSP and nucleolin could form a complex with p53 and Mdm2 by examining the interaction between HAUSP and nucleolin in p53- and Mdm2 depleted cells."
26238070
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"Upon arrival at the mitochondria, p53 underwent rapid deubiquitylation by mitochondrial HAUSP via a stress induced mitochondrial p53 and HAUSP complex."
19066201
sparser
"The interaction of EBNA1 with the N-terminal USP domain appears 10-fold higher in affinity than the interaction of USP7 with p53, which would suggest that EBNA1 may interfere with p53 binding to USP7 and thus promote cell cycle progression and prevent apoptosis."
15359630
sparser
"USP7 interacts with p53 at two closely spaced USP7 binding sites and both sites are needed for USP7 binding [ xref ]."
25659156
sparser
"ABRO1 is upregulated following DNA damage and acts to selectively stabilize p53 by facilitating the interaction of p53 with the deubiquitinase USP7."
25283148
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"Co-immunoprecipitation assay is used to explore the interaction between USP7 and p53."
35538032
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"For example, USP7 and USP10 bind to and deubiquitylate their substrate p53 to mediate its role for suppression of cell propagation upon cellular stresses by counteracting its degradation ."
31745110
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"In full-length USP7 the leaving ubiquitin has a poor affinity compared to the p53 peptide, so we expect Ub to leave first (Step 4), leaving p53 bound to USP7, enabling a change due to the additional binding site (Step 5)."
30651545
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"The p53 release (Step 6) is modelled here as the last step in order to let USP7 return to the ground state, but given the tight interaction (160nM) and the protein concentrations found in cells the p53 and USP7 complex may last longer in vivo."
30651545
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"In animal, USP7, USP10 and USP42 bind to and deubiquitylate the substrate p53 to counteract its degradation ."
31745110
sparser
"Colorectal cancer (CRC) progression relies on myeloid leukemia factor 2 (MLF2), which disrupts the USP7-p53 deubiquitination complex, promoting tumorous growth xref ."
39475222
sparser
"To promote the survival of EBV latently-infected cells with DNA damage, EBNA1 blocks the p53-USP7 interaction, which results in malignant transformation [ xref , xref , xref ]."
32176739
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"However, the identification of a complex of TSPY1, USP7, and p53 suggested that unlike the binding of TSPYL5 with USP7, the binding of TSPY1 to USP7 did not exclude the binding of USP7 to p53, which was supported by the finding that TSPY1 could interact with non-p53-specific binding domains of USP7."
29748603
biogrid
No evidence text available
20816748
reach
"USP7 can bind Mdm2 or p53 via its N-terminal and C-terminal regions in a mutually exclusive manner, which consequently stabilizes the two proteins by removing ubiquitin."
28406480
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"This phenomenon, together with the promotion of TSPYL5 expression as a transcription factor, impairs the interaction of USP7 and p53 to increase ubiquitin mediated p53 degradation."
29748603
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"P53 also interacts with USP7 to promote its nuclear translocation and positively regulates ferroptosis by modifying histones (see below) [133] ."
33915157
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"Intriguingly, overexpression of RORα increased the interaction between p53 and HAUSP ( Figure 3 A ); on the other hand, knockdown of RORα almost completely abolished HAUSP and p53 binding in the prese[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22152482
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"Together, these data suggest that RORα is responsible for enhancing p53 and HAUSP binding that leads to p53 stabilization via p53 deubiquitination."
22152482
reach
"HAUSP was found to interact with p53 and to stabilize p53 through its ubiquitin protease activity [61]."
15865931
sparser
"Cheng et al. found these findings to be consistent with a model in which EBNA1 competitively reduces p53 binding to USP7."
36430864
sparser
"Furthermore, as shown in Figure xref , we also observed a direct interaction between p53 and USP7 in primary hepatocytes with or without insulin treatment, which protects p53 from proteolysis."
25826083
sparser
"We also show that USP7 physically interacts with p53, suggesting that the USP7-mediated de-ubiquitination of p53 inhibits its proteolysis."
25826083
sparser
"Moreover, the interaction between p53 and USP7 was enhanced when SNORD50A/B was deleted while decreased when SNORD50A/B was ectopically expressed (Supplementary Fig.  xref )."
33742136
sparser
"It should be noted that residues 361 GAR AHSS 367 were modeled in the p53 AHSS peptide; however, only 398 AHSS 401 can be modeled in the USP7–NTD:HdmX AHSS complex structure, suggesting a tighter inte[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20713061
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"HDM2 is a primary substrate of USP7, which can bind to the tumor suppressor protein p53 to exert its E3 enzymatic activity and drive p53 ubiquitination and subsequent degradation."
33967786
reach
"Intriguingly, WDR79 knockdown seemed to have a more profound impact on the interaction between USP7 and Mdm2 than the interaction between USP7 and p53."
28406480
sparser
"Interaction between p53 and USP7, a deubiquitinase, decreases H2Bub1 occupancy on the regulatory region of SLC7A11, causing the decrease of SLC7A11 expression [ 38 ]."
35973621
sparser
"However, in SNORD50A/B-deleted p53wt breast cancer cells, GMPS is released into the nucleus and forms a complex with p53 and USP7, leading to deubiquitylation and stabilization of p53 (Fig.  xref )."
33742136
sparser
"Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear."
38879877
sparser
"Intriguingly, WDR79 knockdown seemed to have a more profound impact on the interaction between USP7 and Mdm2 than the interaction between USP7 and p53."
28406480
sparser
"Conversely, supervillin overexpression decreases the association of USP7 and p53 and attenuates USP7-mediated p53 deubiquitination."
23382381
sparser
"As disclosed by biochemical and structural studies, the p53 CTD includes the amino acid residues 359 PGGS R AHSS 367 that harbor two distinct USP7-binding sites while Ser362 and Ser367 are essential for the USP7-p53 binding ( xref )."
32300595
sparser
"HAUSP binding to p53 was recently shown to be regulated by TSPYL5, a protein potentially involved in breast oncogenesis through its competition with p53 for binding to the same region of HAUSP ( xref )."
23483195
sparser
"Co-immunoprecipitation assay is used to explore the interaction between USP7 and p53."
35538032
sparser
"Moreover, USP7 can interact with p53 and promote its expression through mediating its deubiquitination."
35538032
reach
"Upon entry to mitochondria, p53 undergoes prompt deubiquitylation by mitochondrial HAUSP (herpesvirus associated ubiquitin specific protease) via a stress induced p53 and HAUSP complex to generate apoptotically active non ubiquitinated p53."
24177747
sparser
"Mechanistically, USP7 interacts with p53 and removes the ubiquitin from p53, causing p53 stabilization ( xref )."
32300595
sparser
"USP7 interacts with p53 and mediates its deubiquitination."
35538032
sparser
"Co-IP assay revealed that USP7 could interact with p53 ( xref D)."
35538032
biogrid
No evidence text available
11923872
biogrid
No evidence text available
11923872
biogrid
No evidence text available
11923872
biogrid
No evidence text available
11923872
sparser
"The results of the present study were consistent with these previous findings, demonstrating that the deletion and inhibition of HAUSP was associated with p53 upregulation ( xref )."
27899971
biogrid
No evidence text available
31666375
sparser
"Upon stress signals like DNA damage, however, USP7 preferentially binds p53, stabilising it through deubiquitination and allowing the induction of the apoptosis pathway ( Fig. 4 a ) [45,48] ."
28591556
sparser
"TSPYL5, known as a breast cancer risk protein, has been shown to disrupt the p53–USP7 complex [52] , and in vivo results suggest that ABRO1 (FAM175B), a member of the DUB complex BRISC, promotes the p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28591556
sparser
"In response to genotoxic stress or nucleotide deprivation, GMPS is released from the interaction with TRIM21, becomes nuclear and displaces MDM2 from the complex with p53 and USP7, which de-ubiquitylates p53 facilitating its stabilization [ xref , xref ]."
30974870
sparser
"Interestingly, we found that cabozantinib, a multityrosine kinase inhibitor, can disrupt the interaction between USP7 and p53 Y220C proteins and selectively degrade p53 Y220C protein through the CHIP-mediated ubiquitin-proteasomal pathway."
39793887
biogrid
No evidence text available
23388826
reach
"Meanwhile, USP7 could directly interact with and stabilize p53 through deubiquitination [39, 40]."
39343961
sparser
"We show that USP7, a deubiquitinase type involved in the stabilization and removal of lysine-linked ubiquitin from various substrate proteins, physically interacts with p53 Y220C protein ( xref A ) and facilitates the deubiquitination and stabilization of p53 Y220C protein ( xref D and xref A ), and cabozantinib can inhibit the interaction between USP7 and p53 Y220C , resulting in decreased ubiquitination and amount of p53 Y220C protein ( xref )."
39793887
sparser
"Thirdly, destruction of USP7–p53 Y220C interaction by cabozantinib accelerates ubiquitination and subsequent degradation mediated by CHIP ( xref F )."
39793887
biogrid
No evidence text available
23382381
biogrid
No evidence text available
32587091
sparser
"However, in response to DNA damage, USP7 interacts directly with p53, shielding it from ubiquitination, stabilizing it, and triggering the p53‐dependent DNA damage response. [ xref , xref , xref ] "
40289327
reach
"USP7 can bind p53 and Mdm2 (an E3 ubiquitin ligase for p53) and stabilize these proteins by removing the polyubiquitin chains that normally signal degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
23170171
reach
"Meanwhile, our co-IP assays showed that USP7 could directly bind to p53 in each LSCC cell line with or without p53 mutation (Fig. 3C)."
35696794
reach
"The reaction was stopped by the addition of 25 mul 2x SDS sample buffer and analyzed by SDS PAGE.Gel filtration was employed to examine the interaction between p53 and HAUSP."
12507430
sparser
"Importantly, it has been reported that the MDM2-USP7 binding is much stronger than the p53-USP7 binding ( xref ; xref ), which provides a rationale for developing selective inhibitors of MDM2-USP7 interaction without affecting the deubiquitinating effects of USP7 on p53."
32300595
biogrid
No evidence text available
23388826
sparser
"To demonstrate the effect of cabozantinib on the interaction between USP7 and p53 Y220C , we conducted GST-pulldown and co-immunoprecipitation assays in the cells treated with cabozantinib."
39793887
sparser
"Also, we showed a decrease in both exogenous USP7–p53 Y220C interaction in HEK293T cells and endogenous USP7-p53 Y220C interaction in COV362 cells following treatment with cabozantinib ( xref , B and C )."
39793887
sparser
"Collectively, these results demonstrate that cabozantinib can disrupt the interaction between USP7 and p53 Y220C , inducing the CHIP-mediated degradation through K48-linked ubiquitination."
39793887
reach
"USP7 interacts and regulates p53 as well as MDM2 stability by promoting their deubiquitination."
30067985
reach
"The interaction of USP7 with p53 is well characterized, and amino acids 359-367 have been identified as responsible for p53 binding to USP7."
30067985
reach
"We observed that DMOG and the mutation of Pro359 strongly reduced the interaction between p53 and USP7 (XREF_FIG C)."
30067985
reach
"USP7 binding to p53 was recently shown to be regulated by TSPYL5, a protein potentially involved in breast oncogenesis through its competition with p53 for binding to the same region of USP7 (Epping et al., 2011)."
22520753
sparser
"We further showed that the enzymatic activity of HAUSP serves to stabilize cellular p53, and that the interaction between p53 and HAUSP is enhanced in response to DNA damage."
15053880
sparser
"On the one hand, USP7 binds to and directly ubiquitinates p53, preventing its degradation."
40344296
biogrid
No evidence text available
35538032
sparser
"Identification of the in vivo association among RORα, p53, and HAUSP allowed us to hypothesize that RORα might affect p53 stability by regulating the p53-HAUSP binding and the HAUSP-dependent deubiqui[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22152482
sparser
"Intriguingly, overexpression of RORα increased the interaction between p53 and HAUSP ( Figure 3 A ); on the other hand, knockdown of RORα almost completely abolished HAUSP and p53 binding in the prese[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22152482
sparser
"Together, these data suggest that RORα is responsible for enhancing p53 and HAUSP binding that leads to p53 stabilization via p53 deubiquitination."
22152482
biogrid
No evidence text available
21170034
sparser
"Alternatively, during lytic replication, USP7 in the K-RTA-OTUD4-USP7 complex is activated to enable efficient viral replication, while USP7 in the USP7-p53 complex might be specifically targeted by vIRF1 and vIRF3 to negate the antiviral effect of p53 signaling."
38215174
sparser
"P53 first interacts with the tumor necrosis factor (TNF) receptor-associated factor (TRAF) domain and C-terminal (amino acids 880–1050) of USP7, where, by acting as a tumor suppressor, USP7 then ubiquitinates p53 directly and prevents its degradation."
33805973
biogrid
No evidence text available
31492752
biogrid
No evidence text available
30067985
biogrid
No evidence text available
30067985
reach
"Furthermore, as shown in Figure XREF_FIG, we also observed a direct interaction between p53 and USP7 in primary hepatocytes with or without insulin treatment, which protects p53 from proteolysis."
25826083
sparser
"The RORα-dependent p53 stabilization is made possible by the enhanced p53-HAUSP interaction without affecting the p53-MDM2 interaction."
22152482
reach
"Furthermore, an interaction between USP7 and p53 was observed."
39715932
sparser
"Our previous study showed that the p53-HAUSP interaction is enhanced in response to DNA damage (Li et al., 2002) , correlating well with p53 stabilization in vivo."
15053880
sparser
"It is possible that specific HAUSP mutants may be present in tumor cells that only abrogate the p53-HAUSP interaction but not the Mdm2-HAUSP interaction."
15053880
biogrid
No evidence text available
30067985
reach
"We also show that USP7 physically interacts with p53, suggesting that the USP7 mediated de-ubiquitination of p53 inhibits its proteolysis."
25826083
reach
"Once p53 has arrived at the mitochondrial membrane it is rapidly deubiquitinated by the local mitochondrial HAUSP protein via a stress induced mitochondrial p53 and HAUSP complex, creating the apoptotically active, non ubiquitinated p53 protein [XREF_BIBR]."
21037856
biogrid
No evidence text available
30067985
biogrid
No evidence text available
16402859
reach
"The interaction between HAUSP and the p53–Mdm2 complex, leading to p53’s deubiquitination, stands as a seminal example of the role DUBs play in protein stability regulation (32)."
39391247
sparser
"Mitochondrially localized HAUSP forms a stress-induced complex with p53, resulting in p53 de-ubiquitination, which is thought to result in apoptotically active mitochondrial p53 [41] ."
19217357
sparser
"The interaction of USP7 with p53 is well characterized, and amino acids 359–367 have been identified as responsible for p53 binding to USP7 ( xref )."
30067985
sparser
"We observed that DMOG and the mutation of Pro359 strongly reduced the interaction between p53 and USP7 ( xref C)."
30067985
sparser
"Lastly, we investigated the interaction between USP7 and p53 proteins through co-immunoprecipitation."
39715932
sparser
"Furthermore, an interaction between USP7 and p53 was observed."
39715932
biogrid
No evidence text available
16402859
reach
"Moreover, p53 promotes the nuclear translocation of H2Bub1 deubiquitinase USP7 (ubiquitin-specific protease 7) that interacts with, deubiquitinates, and stabilizes p53, functioning as novel regulator of H2Bub1 [138]."
32103754
sparser
"These analyses demonstrate that the N-terminal domain (53–208) of HAUSP stably interacts with a minimal C-terminal peptide (357–382) of p53 (Figure 6B) ."
12507430
sparser
"Gel filtration was employed to examine the interaction between p53 and HAUSP."
12507430
sparser
"In full-length USP7 the leaving ubiquitin has a poor affinity compared to the p53 peptide (Fig.  xref ), so we expect Ub to leave first (Step 4), leaving p53 bound to USP7, enabling a change due to the additional binding site (Step 5)."
30651545
sparser
"The p53 release (Step 6) is modelled here as the last step in order to let USP7 return to the ground state, but given the tight interaction (160 nM) and the protein concentrations found in cells the p53-USP7 complex may last longer in vivo."
30651545
reach
"Upon stress signals like DNA damage, however, USP7 preferentially binds p53, stabilising it through deubiquitination and allowing the induction of the apoptosis pathway ( Fig. 4 a ) [45,48] ."
28591556
reach
"TSPYL5, known as a breast cancer risk protein, has been shown to disrupt the p53–USP7 complex [52] , and in vivo results suggest that ABRO1 (FAM175B), a member of the DUB complex BRISC, promotes the p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28591556
reach
"Previous studies demonstrated that EBNA1 regulates USP7 interactions with MDM2 and p53 to control of cell cycle [47]."
39821265
reach
"From a mechanistic perspective, upon activation, TP53 binds directly to the SLC7A11 promoter or interacts with ubiquitin-specific peptidase 7, reducing histone H2B monoubiquitination on the promoter, thus decreasing SLC7A11 expression and lessening cysteine uptake (thereby decreasing GSH synthesis), which promotes ferroptosis [51–53]."
39543600
reach
"Interaction between p53 and USP7, a deubiquitinase, decreases H2Bub1 occupancy on the regulatory region of SLC7A11, causing the decrease of SLC7A11 expression [ 38 ]."
35973621
biogrid
No evidence text available
25283148
biogrid
No evidence text available
17525743
biogrid
No evidence text available
17525743
reach
"Next, to examine whether USP7 interacts with p53, we performed a co-IP assay after etoposide treatment to increase p53 expression."
29795372
reach
"Cheng et al. found these findings to be consistent with a model in which EBNA1 competitively reduces p53 binding to USP7."
36430864
reach
"Some DUBs have additional binding sites with affinity for the target protein that is ubiquitylated (Ventii and Wilkinson, 2008) ; for example, USP7 binds to a peptide sequence present in its substrates p53, MDM2 (murine double minute 2, an oncoprotein) and the Epstein Barr nuclear antigen-1 (Hu et al., 2006) ."
19571111
reach
"Conflicting studies show that binding of p53 to USP7 either promotes the deubiquitination and subsequent stabilization of p53 [XREF_BIBR, XREF_BIBR] or that disruption of USP7 stabilizes p53 [XREF_BIBR, XREF_BIBR]."
20210752
sparser
"USP7 also binds p53 directly; Brooks et al. used a H1299 cell culture model to show USP7 binding to p53 or MDM2 is mutually exclusive [ xref ]."
35008383
sparser
"FAM188B binds to USP7 and destabilizes the USP7-p53 interaction, thereby promoting p53 ubiquitination and degradation ( xref (iv))."
35008383
sparser
"This somewhat surprising finding suggested to us that the functional significance of the USP7-p53 axis in Ewing Sarcoma, and perhaps cancer more broadly, is not completely understood and that improved research tools are needed to enable reliable on-target analysis of USP7 biology."
32210275
biogrid
No evidence text available
31647545
hprd
No evidence text available
16474402
hprd
No evidence text available
11923872
reach
"USP7 binds to p53, which contributes to its deubiquitination and stabilization."
20210752
reach
"Monoubiquitylation of the tumor suppressor p53 mediated by MDM2 promotes its mitochondrial apoptosis, however, the apoptotically active non ubiquitylated p53 can also be generated via the p53 and USP7 complex [XREF_BIBR]."
20210752
biogrid
No evidence text available
31647545
reach
"Furthermore, EBNA-1-USP7 interaction prevents the binding of USP7 to p53 and thereby diminishes p53 stabilization."
30807924
reach
"Alternatively, during lytic replication, USP7 in the K-RTA-OTUD4-USP7 complex is activated to enable efficient viral replication, while USP7 in the USP7-p53 complex might be specifically targeted by vIRF1 and vIRF3 to negate the antiviral effect of p53 signaling."
38215174
reach
"USP7 also binds the tumour suppressor protein p53 and the ubiquitin ligase MDM2 (amongst other proteins, including MDMX and FoxO4A) and in so doing, removes ubiquitin moieties that would otherwise target these substrate proteins for degradation by the proteasome (XREF_FIG)."
29642420
sparser
"HAUSP (herpesvirus-associated ubiquitin-specific protease) binds to the transcription factor and tumor suppressor p53 ( xref )."
35302693
reach
"HAUSP directly binds to and deubiquitylates p53 both in vivo and in vitro."
16402859
reach
"USP7 binds and stabilizes p53 XREF_BIBR, and EBNA1 was found to block the USP7-p53 interaction in vitro by competing for the same binding pocket on USP7 XREF_BIBR - XREF_BIBR."
18833293
reach
"The observation that HAUSP can directly interact with and deubiquitylate both p53 and MDM2 creates a conundrum : how can HAUSP stabilize p53 while at the same time being able to stabilize MDM2, which is primarily responsible for the destruction of p53?"
16402859
reach
"To facilitate formation of a stable p53 and HAUSP complex, we generated a chimeric protein with the C-terminus of the HAUSP TRAF like domain (residues 53-199) fused to ten amino acids corresponding to p53 residues 359-368."
16402859
reach
"The fact that both a p53 C-terminal peptide fragment and a short-peptide sequence preceding the acidic domain of MDM2 bind to the N-terminal TRAF like domain of HAUSP raised an intriguing possibility : HAUSP binding by p53 and by MDM2 might be mutually exclusive."
16402859
reach
"To assess the strength of HAUSP binding by p53 and by MDM2, we measured the binding affinity between the HAUSP TRAF like domain (residues 53-206) and a p53 peptide (residues 351-382) or an MDM2 peptide (residues 208-242) using isothermal titration calorimetry (ITC)."
16402859
reach
"Despite these common features, important differences exist for HAUSP binding by p53 and by MDM2, which explain the competitive edge of MDM2 over p53."
16402859
reach
"Second, MDM2 binding to HAUSP was found to be mutually exclusive with p53 binding to HAUSP."
16402859
reach
"A minimal HAUSP binding peptide derived from MDM2 efficiently displaced p53 from the p53 and HAUSP complex in a competition assay and formed a stable HAUSP and MDM2 complex."
16402859
sparser
"Via these interactions, MLF2 inhibits the binding of USP7 to p53 and antagonizes USP7‐mediated deubiquitination of p53, thereby leading to p53 destabilization."
37438558
reach
"Although HAUSP can bind to p53, our competition data suggest that HAUSP exhibits a higher binding affinity for MDM2, which likely translates into a stronger preference for MDM2 deubiquitylation and stabilization."
16402859
sparser
"Mechanistically, MLF2 binds to USP7 and p53 and disrupts the USP7–p53 interaction."
37438558
reach
"Upon arrival at the mitochondria, our data suggest that p53 undergoes rapid deubiquitylation by mitochondrial HAUSP via a stress induced mitochondrial p53 and HAUSP complex."
17268548
sparser
"The N-terminal domain of USP7 is involved in p53-USP7 interactions, and also contains a TRAF domain and an EBNA1 binding domain."
32354135
reach
"The interactions between HAUSP and p53 or MDM2 are likely to be more complex in vivo, not only due to the presence of multiple binding sites in MDM2 but also because of the oligomeric nature of p53 and possibly HAUSP."
16402859
sparser
"USP7 binds and stabilizes p53 xref , and EBNA1 was found to block the USP7-p53 interaction in vitro by competing for the same binding pocket on USP7 xref – xref ."
18833293
sparser
"Thus, EBNA1 can displace USP7 binding with p53 to protect the cells from p53-mediated apoptosis, probably contributing to cell immortalization, proliferation, and survival following infection with EBV xref , xref ."
30555548
sparser
"17 , 18 Originally, ectopic overexpression studies revealed that USP7 can directly bind to and deubiquitinate p53, leading to its stabilization."
36952348
sparser
"Upon stress signals such as DNA damage, the USP7-Mdm2 interaction is compromised through ataxia telangiectasia mutated (ATM)-mediated phosphorylation, and USP7 becomes preferentially associated with p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36952348
biogrid
No evidence text available
37353627
biogrid
No evidence text available
37353627
sparser
"Furthermore, EBNA-1–USP7 interaction prevents the binding of USP7 to p53 and thereby diminishes p53 stabilization ( xref )."
30807924
sparser
"By performing an immunoprecipitation assay, we showed that the interaction between exogenously expressed USP7 and p53 was strongly reduced when MLF2 was simultaneously expressed (Figure  xref )."
37438558
sparser
"In addition, MLF2 knockdown increased, whereas MLF2 overexpression decreased, the interaction between endogenous USP7 and p53 (Figure  xref ), indicating that MLF2 inhibits the USP7–p53 binding."
37438558
sparser
"In support of this, MLF2 was shown to dose‐dependently decrease the association of USP7 and p53 in vitro (Figure  xref )."
37438558
sparser
"Abraxas brother 1 (ABRO1), a component of the BRCC36-containing isopeptidase complex (BRISC), stabilizes p53 by facilitating the interaction of p53 with USP7 to reduce p53 ubiquitination [ xref ]."
28446729
sparser
"Correlated with the inhibitory effect of MLF2 on the USP7─p53 binding, MLF2 was shown to compromise USP7‐catalyzed deubiquitination of p53 in vitro (Figure  xref )."
37438558
sparser
"These include: (1) TRAF4-Akt/NF-κB-Glut1/HK2/RSK4/Slug in the proliferation and metastasis of lung and breast cancer cells as well as the migration and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells (HCC) ( xref , xref , xref ); (2) TGFβ-TβRI-TRAF4-Smurf1/Smurf2/USP15-SMAD2/TAK1-N-cadherin/Fibronectin/Vimentin/SMA in the migration, EMT, and metastasis of breast cancer cells ( xref , xref ); (3) SRC3-TRAF4-mediated inhibition of the USP7-p53 interaction, leading to the loss of p53 deubiquitination/stabilization and thus the resistance to cytotoxic drugs and stress in breast cancer ( xref ); (4) NGF-TrkA-TRAF4-Akt/p38-IL-6/Integrins/COX2 in the metastasis of prostate cancer cells ( xref ); (5) TNFα-TRAF4/TRAF2-NF-κB1 in the survival and proliferation of breast cancer cells ( xref ); (6) TRAF4-mediated up-regulation and nuclear translocation of β-catenin in the Wnt/β-catenin-cyclin D1/c-myc/Bcl-2/MMPs pathway that promote the growth and migration of OSCC and breast cancer cells ( xref , xref ); (7) TRAF4-mTOR-p70S6K-S6 in the proliferation of breast cancer cells ( xref ); and (8) the TRAF4-phosphoinositide (PIP) interaction at tight junctions that favors breast cancer cell migration ( xref )."
30294322
sparser
"Together, these data suggest that MLF2 reduces the binding of USP7 to p53 and thus attenuates USP7‐mediated deubiquitination of p53, resulting in the destabilization of p53."
37438558
sparser
"By performing an immunoprecipitation assay, we also showed that when cells were treated with doxorubicin, the interaction between USP7 and MLF2 was significantly decreased, whereas the USP7–p53 interaction was noticeably increased (Figure  xref )."
37438558
sparser
"Depletion of nucleolin did not affect the interaction between HAUSP and p53 in both normal and DNA damaged conditions ( xref )."
26238070
sparser
"Mechanistically, by binding to UPS7, MLF2 disrupts the USP7–p53 interaction and reduces the deubiquitinating activity of USP7 toward p53, thereby resulting in the destabilization of p53."
37438558
sparser
"A number of proteins have been reported to interact with USP7 and regulate its activity toward Mdm2 or p53. [ xref ] For instance, death domain associated protein (Daxx) promotes the binding of USP7 to Mdm2 and enhances Mdm2‐dependent p53 degradation. [ xref ] In addition, testis‐specific protein Y‐encoded like 5 (TSPYL5) and Epstein‐Barr virus nuclear antigen 1 (EBNA1) compete with p53 for binding to the TRAF‐like domain of USP7, thereby suppressing the function of p53. [ xref , xref ] Moreover, Abraxas brother 1 (ABRO1) stabilizes p53 by facilitating the interaction of p53 with USP7. [ xref ] In this study, we show that MLF2 binds to both N‐terminal TRAF‐like domain and C‐terminal UBL4‐5 of USP7."
37438558
sparser
"USP7 specifically binds to and stabilizes p53 and can lead to p53-dependent cell-cycle arrest and apoptosis [ 32 •• ]."
21411309
reach
"HAUSP binding to p53 was recently shown to be regulated by TSPYL5, a protein potentially involved in breast oncogenesis through its competition with p53 for binding to the same region of HAUSP."
23483195
sparser
"Since these two USP7 regions are also important for p53 binding, [ xref , xref , xref ] it is reasonable that MLF2 may disrupt the interaction between USP7 and p53 in a competitive manner."
37438558
sparser
"HDM2 is a primary substrate of USP7, which can bind to the tumor suppressor protein p53 to exert its E3 enzymatic activity and drive p53 ubiquitination and subsequent degradation."
33967786
sparser
"Such effects are interfered with by the EBV EBNA1 protein through competitive inhibition of the p53–USP7 interaction, providing a mechanism by which EBV can increase cell survival [ 33 •• ]."
21411309
sparser
"USP7 binds p53 through p53 regulatory sequences known to modulate p53–DNA interactions and this interaction was recently shown to stimulate p53 binding to its recognition sites [ 38 • ]."
21411309
sparser
"Holowaty and Frappier [ xref ] showed that binding of EBNA1 to USP7 disrupts the USP7-p53 interaction."
20210752
sparser
"Conflicting studies show that binding of p53 to USP7 either promotes the deubiquitination and subsequent stabilization of p53 [ xref , xref ] or that disruption of USP7 stabilizes p53 [ xref , xref ]."
20210752
sparser
"By disrupting the p53-USP7 interaction, EBNA1 would be expected to promote cell-cycle progression and prevent apoptosis, which could be important for the host cell immortalization typical of EBV [ xref ]."
18687060
reach
"This model has been consolidated by structural and biochemical data which revealed that while both Mdm2 and p53 associate with USP7 in a mutually exclusive manner, USP7 has a higher binding affinity f[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17961905
sparser
"Previous reports have unveiled N-terminal or C-terminal region of USP7 is required for substrates binding and interacting like Yki [ xref ] and GATA1 [ xref ], whereas both regions are needed for USP7 and p53 interaction [ xref ]."
35931679
sparser
"The interaction between p53 and USP7 reduces the occupancy of H2Bub1 at the regulatory region of SLC7A11, leading to transcriptional repression of SLC7A11and enhancing the ferroptosis induction sensitivity of cells ( xref )."
41235664
sparser
"This difference in the USP7–NTD interaction is thought to underlie the observations that EBNA1 can interfere with p53–USP7 interactions in vitro and p53 stabilization in vivo [ 33 •• ,48 ], properties[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21411309
sparser
"USP7 binds to p53, which contributes to its deubiquitination and stabilization."
20210752
reach
"USP7 was also shown to be involved in the stress-induced p53 translocation to the mitochondria since a stress-inducible USP7-p53 complex was formed at the mitochondria resulting in p53 de-ubiquitinati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17961905
reach
"USP7 binds to p53 and mdm2, stabilizing the proteins."
34888589
sparser
"USP7 is another well-known cancer-associated DUB that interacts with the tumor suppressor gene p53 and USP7 deubiquitinating function may protect cells from apoptosis."
32512887
sparser
"The p53-USP7 interaction is thought to involve the N-terminal portion of USP7 which also contains a TRAF domain (tumor necrosis factor-receptor associated factor) which interacts in vitro with the human TRAF proteins [114] and EBNA1 protein of EBV [115,116]."
15359630
biogrid
No evidence text available
20713061
reach
"Herpesvirus-associated ubiquitin-specific protease (HAUSP) interacts with and stabilizes p53 by deubiquitinating p53 [112]."
38132337
sparser
"DNA damage increases the interaction between p53 and USP7 [ xref ]."
23151129
sparser
"Concomitantly, the interaction between USP7 and p53 increases."
23151129
reach
"USP7 interacts with p53 at two closely spaced USP7 binding sites and both sites are needed for USP7 binding [XREF_BIBR]."
25659156
reach
"Previous reports have unveiled N-terminal or C-terminal region of USP7 is required for substrates binding and interacting like Yki [50] and GATA1 [54], whereas both regions are needed for USP7 and p53 interaction [55]."
35931679
sparser
"HAUSP interacts with p53 and removes the ubiquitin from p53, resulting in p53 stabilization."
34072267
sparser
"Considering that USP7 is a p53 deubiquitinase, KSHV ORF45 inhibits the interactions between USP7 and p53 by binding to p53."
39664521
sparser
"However, in the context of DNA damage, HDM2 dissociates from the USP7–DAXX complex, resulting in self-ubiquitination and subsequent degradation of HDM2, and then USP7 binds to p53 ( xref )."
39664521
sparser
"Next, to examine whether USP7 interacts with p53, we performed a co-IP assay after etoposide treatment to increase p53 expression."
29795372
sparser
"For example, while the wild-type p53 (residues 325–367) formed a stable complex with HAUSP (residues 53–206) as judged by their co-elution on gel filtration ( xref A, upper-right panel), the mutant p53 (S362A) and HAUSP (residues 53–206) did not interact with each other ( xref A, lower-right panel)."
16402859
sparser
"To elucidate the mechanism by which p53 recognizes HAUSP, we launched rigorous trials aimed at crystallizing the HAUSP TRAF-like domain bound to a synthetic p53 peptide."
16402859
sparser
"To facilitate formation of a stable p53–HAUSP complex, we generated a chimeric protein with the C-terminus of the HAUSP TRAF-like domain (residues 53–199) fused to ten amino acids corresponding to p53 residues 359–368."
16402859
sparser
"The structure of the HAUSP TRAF-like domain bound to p53 (residues 359–368) was determined at 2.3-Å resolution by molecular replacement ( xref ; xref B)."
16402859
sparser
"This result indicates that the same domain of HAUSP that interacts with p53 is also responsible for binding to MDM2."
16402859
sparser
"Deletion analyses have shown that the C-terminal regulatory region of p53 (residues 351–382) binds USP7 and that the N-terminal domain (residues 53–208) of USP7 is sufficient for this interaction xref , xref ."
20885946
sparser
"Similar to what we observed with full-length USP7, the USP7-CTD stimulated sequence-specific DNA binding by p53, as compared to the BSA control, suggesting that it is largely responsible for the p53-USP7 interaction that results in increased p53 sequence-specific DNA binding."
20885946
sparser
"These results are consistent with the in vitro observation that the CTD of USP7 is sufficient to stimulate p53-DNA binding, and together these observations suggest that the stimulation of p53 DNA-binding by USP7 leads to enhanced p53 function."
20885946
sparser
"Since the p53 regulatory region contributes to DNA interactions by increasing the sliding of p53 on DNA and such sliding has been suggested to result in decreased detectable binding to short DNA fragments (such as used in our in vitro studies), it is likely that USP7 interactions with p53 C-terminal sequences result in decreased DNA sliding xref ."
20885946
sparser
"Mutually Exclusive HAUSP Binding by p53 and by MDM2."
16402859
sparser
"On a molecular level, the best-described interaction of USP7 is with the transcription factor p53, which regulates the expression of many genes required for DNA repair, cell cycle arrest or apoptosis during genomic stress [ xref ]."
38672118
sparser
"Although the USP7-p53 axis has been characterized extensively in cancer cells, xref , xref , xref our findings broaden the relevance of this signaling pathway to post-mitotic neurodevelopment."
39862434
sparser
"The fact that both a p53 C-terminal peptide fragment and a short-peptide sequence preceding the acidic domain of MDM2 bind to the N-terminal TRAF-like domain of HAUSP raised an intriguing possibility: HAUSP binding by p53 and by MDM2 might be mutually exclusive."
16402859
sparser
"In contrast, p53-DNA complexes migrated similarly in the presence or absence of USP7 (compare shifted bands in xref ), suggesting that USP7 does not remain stably associated with DNA-bound p53."
20885946
sparser
"To assess the strength of HAUSP binding by p53 and by MDM2, we measured the binding affinity between the HAUSP TRAF-like domain (residues 53–206) and a p53 peptide (residues 351–382) or an MDM2 peptide (residues 208–242) using isothermal titration calorimetry (ITC)."
16402859
sparser
"Intriguingly, the minimal MDM2 fragment (residues 223–232) required for binding to HAUSP exhibited little sequence homology to the p53 fragment that interacts with the same domain of HAUSP."
16402859
sparser
"Gly361 in p53, which does not directly interact with HAUSP, is substituted by Val228 in MDM2, resulting in additional van der Waals contacts with Trp165 and Glu162 in HAUSP ( xref B)."
16402859
reach
"Surprisingly, however, we have found that direct interaction between HAUSP and p53 is not absolutely required for it to antagonize efficiently Mdm2 mediated ubiquitination of p53 and that HAUSP is capable of enzymatically functioning in trans on p53 by using Mdm2 as a bridge."
17525743
sparser
"Despite these common features, important differences exist for HAUSP binding by p53 and by MDM2, which explain the competitive edge of MDM2 over p53."
16402859
biogrid
No evidence text available
29795372
biogrid
No evidence text available
29795372
biogrid
No evidence text available
34795231
reach
"The finding that the herpesvirus-associated ubiquitin-specific protease (HAUSP) could bind to and stabilize p53 added yet another layer of regulation to the p53 ubiquitination pathway and was one of t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16455486
reach
"In response to DNA damage, HAUSP interacts with and stabilizes p53."
21372216
reach
"However, in EBV infected cells EBNA-1 can efficiently block the interaction between HAUSP and p53 resulting in ubiquitin-proteasome mediated degradation of p53."
21372216
sparser
"Second, MDM2 binding to HAUSP was found to be mutually exclusive with p53 binding to HAUSP."
16402859
sparser
"P53 can form a nuclear p53-USP7 protein complex with de-ubiquitin specific peptidase 7 (USP7), further reduces the level of histone H2B monoubiquitylation (H2Bub1, a histone modification) mediated expression of SLC7A11, ultimately leading to ferroptosis ( xref )."
34977044
sparser
"Recent studies identified a deubiquitylating enzyme called HAUSP (herpesvirus-associated ubiquitin-specific protease) that can bind to p53, stabilize the protein, and promote cell death and cell growth arrest."
20076526
sparser
"Although HAUSP can bind to p53, our competition data suggest that HAUSP exhibits a higher binding affinity for MDM2, which likely translates into a stronger preference for MDM2 deubiquitylation and stabilization."
16402859
sparser
"To study the structural details of HAUSP–p53 interactions, the authors mutated different amino acid residues in the p53 binding site and identified a short stretch of five amino acids required for binding."
20076526
sparser
"This structure shows that the p53 peptide binds to HAUSP's shallow groove and reveals how many of the amino acids previously identified as important for HAUSP–p53 binding interact with specific p53 residues."
20076526
sparser
"In response to genotoxic stress, USP7 binds and deubiquitylates p53 thereby protecting it from proteasome-mediated degradation."
19834552
sparser
"As a result, EBNA1 interferes with the binding and stabilization of p53 by USP7 and with p53-mediated apoptosis in response to DNA damage xref , xref ."
19834552
sparser
"Interestingly, STIP knock down seem to have a more profound impact on the interaction between USP7 and Mdm2 than the interaction between USP7 and p53."
26460617
sparser
"Consistent with this, our results reveal that STIP knock down have a more profound impact on the interaction between USP7 and Mdm2 than the interaction between USP7 and p53 (Figure xref )."
26460617
biogrid
No evidence text available
17268548
biogrid
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26238070
biogrid
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26238070
reach
"Via these interactions, MLF2 inhibits the binding of USP7 to p53 and antagonizes USP7-mediated deubiquitination of p53, thereby leading to p53 destabilization."
37438558
reach
"In addition, MLF2 knockdown increased, whereas MLF2 overexpression decreased, the interaction between endogenous USP7 and p53 (Figure 4G,H), indicating that MLF2 inhibits the USP7–p53 binding."
37438558
reach
"Together, these data suggest that MLF2 reduces the binding of USP7 to p53 and thus attenuates USP7‐mediated deubiquitination of p53, resulting in the destabilization of p53.To further determine whether MLF2 regulates the p53 response to DNA damage, HCT116 cells with knockdown or overexpression of MLF2 were treated with the DNA‐damage‐inducing agent doxorubicin."
37438558
reach
"Since these two USP7 regions are also important for p53 binding, 21 , 25 , 42 it is reasonable that MLF2 may disrupt the interaction between USP7 and p53 in a competitive manner.MLF2 belongs to the myeloid leukemia factor family, which is involved in myelodysplastic syndrome and acute myeloid leukemia."
37438558
reach
"Upon arrival at the mitochondrion, p53 undergoes rapid deubiquitination by resident mitochondrial HAUSP via a stress induced mitochondrial p53 and HAUSP complex to generate the apoptotically active non ubiquitinated p53."
27308326
sparser
"Recently, it was discovered that herpesvirus-associated ubiquitin-specific protease (HAUSP) in human interacts with p53 protein, and removes the ubiquitin from ubiquitinated p53."
14719112