IndraLab

Statements

TP53 binds USP7. 214 / 235
29 2 | 1 77 105
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
"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
reach
"USP7 interacts and regulates p53 as well as MDM2 stability by promoting their deubiquitination (Li et al., 2002; Ma et al., 2010)."
30067985
sparser
"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
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
sparser
"Moreover, USP7 can interact with p53 and promote its expression through mediating its deubiquitination."
35538032
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
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
reach
"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
reach
"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
sparser
"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
biogrid
No evidence text available
16402859
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
"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
"USP7 also interacts with the polyubiquitinated p53 and promotes p53 deubiquitination and stability ( xref )."
20531303
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
biogrid
No evidence text available
24462112
reach
"We observed that DMOG and the mutation of Pro359 strongly reduced the interaction between p53 and USP7."
30067985
biogrid
No evidence text available
11923872
reach
"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
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
"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
"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
biogrid
No evidence text available
16474402
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
"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
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
"34 This action is functionally similar to that previously reported for the viral protein EBNA1, which competitively inhibits HAUSP and p53 complex formation."
29967688
sparser
"It was reported that the affinity of USP7-EBNA1 was 10-fold higher than USP7-p53, implying the strong binding of USP7-EBNA1 (Saridakis et al., 2005)."
31921057
biogrid
No evidence text available
11923872
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
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
biogrid
No evidence text available
26238070
sparser
"In this study, we found that USP7 interacts with p53 protein."
35127703
sparser
"RORα promotes interactions between p53 and USP7 but does not affect interactions between p53 and MDM2 (ref. xref )."
25283148
biogrid
No evidence text available
17268548
reach
"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
reach
"The interaction between p53 and USP7 can be disrupted by EBNA1."
33505922
trips
"Indeed, this mutant p53 protein can be degraded by Mdm2 but fails to interact with HAUSP both in vitro and in vivo."
17525743
reach
"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
"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
hprd
No evidence text available
11923872
reach
"Furthermore, EBNA-1-USP7 interaction prevents the binding of USP7 to p53 and thereby diminishes p53 stabilization."
30807924
reach
"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
reach
"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
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 (Sheng et al., 2006)."
30067985
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
"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
"In response to genotoxic stress, USP7 binds and deubiquitylates p53 thereby protecting it from proteasome mediated degradation."
19834552
biogrid
No evidence text available
26238070
sparser
"Mechanistically, USP7 interacts with p53 and removes the ubiquitin from p53, causing p53 stabilization ( 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
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
"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
"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
"This result indicates that the same domain of HAUSP that interacts with p53 is also responsible for binding to MDM2."
16402859
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
reach
"We therefore examined the effect of ABRO1 on the interaction between USP7 and p53."
25283148
reach
"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
reach
"USP7 interacts and regulates p53 as well as MDM2 stability by promoting their deubiquitination."
30067985
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
reach
"Second, MDM2 binding to HAUSP was found to be mutually exclusive with p53 binding to HAUSP."
16402859
reach
"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
"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
"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
biogrid
No evidence text available
21845734
sparser
"Co-immunoprecipitation assay is used to explore the interaction between USP7 and p53."
35538032
sparser
"Concomitantly, the interaction between USP7 and p53 increases."
23151129
biogrid
No evidence text available
17525743
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
reach
"In addition, USP7 can interact indirectly with p53, using Mdm2 as a bridge, resulting in the formation of USP7-Mdm2-p53 complexes."
26460617
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
"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
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
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
"HAUSP interacts with p53 and removes the ubiquitin from p53, resulting in p53 stabilization."
34072267
biogrid
No evidence text available
23388826
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
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
"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
reach
"In animal, USP7, USP10 and USP42 bind to and deubiquitylate the substrate p53 to counteract its degradation ."
31745110
reach
"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
"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
biogrid
No evidence text available
22084066
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
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
"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
"We observed that DMOG and the mutation of Pro359 strongly reduced the interaction between p53 and USP7 ( Figure 5 C)."
30067985
sparser
"Holowaty and Frappier [ xref ] showed that binding of EBNA1 to USP7 disrupts the USP7-p53 interaction."
20210752
reach
"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
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
"We therefore examined the effect of ABRO1 on the interaction between USP7 and p53."
25283148
sparser
"USP7 binds to p53, which contributes to its deubiquitination and stabilization."
20210752
reach
"RORalpha promotes interactions between p53 and USP7 but does not affect interactions between p53 and MDM2."
25283148
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
"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
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
sparser
"Next, to examine whether USP7 interacts with p53, we performed a co-IP assay after etoposide treatment to increase p53 expression."
29795372
sparser
"ABRO1 is upregulated following DNA damage and acts to selectively stabilize p53 by facilitating the interaction of p53 with the deubiquitinase USP7."
25283148
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
"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
"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
"HAUSP was found to interact with p53 and to stabilize p53 through its ubiquitin protease activity [61]."
15865931
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
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
biogrid
No evidence text available
23382381
sparser
"The interaction between p53 and USP7 can be disrupted by EBNA1 ( xref )."
33505922
sparser
"We also show that USP7 physically interacts with p53, suggesting that the USP7-mediated de-ubiquitination of p53 inhibits its proteolysis."
25826083
hprd
No evidence text available
16474402
reach
"Next, to examine whether USP7 interacts with p53, we performed a co-IP assay after etoposide treatment to increase p53 expression."
29795372
reach
"We observed that DMOG and the mutation of Pro359 strongly reduced the interaction between p53 and USP7 (XREF_FIG C)."
30067985
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
biogrid
No evidence text available
26460617
reach
"USP7 binds to p53 and mdm2, stabilizing the proteins."
34888589
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
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
biogrid
No evidence text available
25283148
sparser
"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
sparser
"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
reach
"USP7 interacts with and deubiquitinates p53, thereby stabilizing and protecting it from Mdm2 mediated degradation [XREF_BIBR]."
18687060
reach
"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
reach
"USP7 binds to p53, which contributes to its deubiquitination and stabilization."
20210752
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
reach
"However, in SAMe-D cells the levels of HAUSP were higher, and there was a functional interaction between p53 and HAUSP."
20815019
biogrid
No evidence text available
11923872
reach
"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
biogrid
No evidence text available
16474402
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
"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
"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
reach
"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
reach
"We also show that USP7 physically interacts with p53, suggesting that the USP7 mediated de-ubiquitination of p53 inhibits its proteolysis."
25826083
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
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
"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
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
"In contrast, USP7-p53 interaction was not affected when control siRNA was transfected."
25283148
sparser
"FAM188B binds to USP7 and destabilizes the USP7-p53 interaction, thereby promoting p53 ubiquitination and degradation ( xref (iv))."
35008383
sparser
"In response to genotoxic stress, USP7 binds and deubiquitylates p53 thereby protecting it from proteasome-mediated degradation."
19834552
biogrid
No evidence text available
16402859
sparser
"Depletion of nucleolin did not affect the interaction between HAUSP and p53 in both normal and DNA damaged conditions ( xref )."
26238070
reach
"Further examination using a sequential immunoprecipitation assay confirmed that ABRO1, p53 and USP7 were present in the same complex (XREF_FIG)."
25283148
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
biogrid
No evidence text available
23388826
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
"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
biogrid
No evidence text available
21170034
sparser
"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
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
"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
"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
sparser
"Therefore, the identification and investigation of proteins interacting with HAUSP is of significance for deeply understanding p53 signal pathways."
31647545
biogrid
No evidence text available
14506283
sparser
"Mutually Exclusive HAUSP Binding by p53 and by MDM2."
16402859
sparser
"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
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
"Conversely, supervillin overexpression decreases the association of USP7 and p53 and attenuates USP7-mediated p53 deubiquitination."
23382381
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
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
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
11923872
reach
"USP7 interacts with p53 at two closely spaced USP7 binding sites and both sites are needed for USP7 binding [XREF_BIBR]."
25659156
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
biogrid
No evidence text available
17525743
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
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
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
biogrid
No evidence text available
16845383
sparser
"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
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
"The p53-USP7 interaction is also negatively regulated by the TSPYL5 inhibitor protein ( xref )."
32850836
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
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
biogrid
No evidence text available
24462112
sparser
"We further show that ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7."
25283148
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
"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
"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
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
"DNA damage increases the interaction between p53 and USP7 [ xref ]."
23151129
reach
"Upon arrival at the mitochondria, p53 underwent rapid deubiquitylation by mitochondrial HAUSP via a stress induced mitochondrial p53 and HAUSP complex."
19066201
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
sparser
"Gel filtration was employed to examine the interaction between p53 and HAUSP."
12507430
reach
"USP7 can bind directly to Mdm2 or p53 in a mutually exclusive manner."
26460617
reach
"HAUSP directly binds to and deubiquitylates p53 both in vivo and in vitro."
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
"USP7 interacts with p53 at two closely spaced USP7 binding sites and both sites are needed for USP7 binding [ xref ]."
25659156
sparser
"TSPYL5 disrupts the p53-USP7 interaction, leading to increased polyubiquitination and degradation of p53."
32850836
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
reach
"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
reach
"In response to DNA damage, HAUSP interacts with and stabilizes p53."
21372216
reach
"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
biogrid
No evidence text available
20816748
reach
"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
"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
"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
"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
"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
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
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
reach
"Co-immunoprecipitation assay is used to explore the interaction between USP7 and p53."
35538032
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 ( Sheng et al., 2006 )."
30067985
sparser
"Second, MDM2 binding to HAUSP was found to be mutually exclusive with p53 binding to HAUSP."
16402859
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
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
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
sparser
"Furthermore, EBNA-1–USP7 interaction prevents the binding of USP7 to p53 and thereby diminishes p53 stabilization ( xref )."
30807924
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
"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
"We observed that DMOG and the mutation of Pro359 strongly reduced the interaction between p53 and USP7 ( xref C)."
30067985
sparser
"To further investigate the relationship between USP7 and apoptotic proteins, the potential interaction between USP7 and p53 was evaluated in H9C2 cells."
35127703
biogrid
No evidence text available
17380154
biogrid
No evidence text available
20713061