IndraLab

Statements

USP7 binds MDM2. 174 / 194
24 4 | 1 74 71
sparser
"They find that, before stress signaling, USP7 binds and deubiquitylates MDM2, thus stabilizing MDM2 and promoting p53 degradation."
24507714
biogrid
No evidence text available
28196907
sparser
"On the contrary, compared to wild-type and the KRKR mutant, the KQKQ mutant exhibited increased interaction with HAUSP in both the nucleus and the cytoplasm, suggesting that nuclear translocation of MDM2 is not required for HAUSP interaction with MDM2, at least in this experimental setting ( xref )."
28196907
reach
"USP7 can directly bind Mdm2 in vitro [XREF_BIBR]."
18687060
reach
"Previous studies had indicated that Daxx plays a role in regulating posttranslational stability of the p53 tumor suppressor through interaction with the Mdm2 and Hausp complex [XREF_BIBR]."
28301594
reach
"Under non stressed conditions, for example, the MDM2 and MDMX complex also binds to the deubiquitinating protein HAUSP, which stabilizes both MDM2 and MDMX."
23002429
sparser
"Expression of RASSF1 , the product of which disrupts the interaction between MDM2 and HAUSP was significantly up-regulated in the clinical PNI samples."
27665737
reach
"USP7 can bind directly to Mdm2 or p53 in a mutually exclusive manner."
26460617
reach
"We then employed co-immunoprecipitation to identify possible changes in the binding of USP7 to Mdm2 and p53."
28406480
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
sparser
"Mapping HAUSP–MDM2 Interactions."
16402859
sparser
"However, the deubiquitinase HAUSP interacted with acetylation-mimetic mutants of MDM2 with greater affinity than it did with wild-type MDM2 in 293T cells ( xref ), which might in part explain the reduced autoubiquitination status for the acetylation-mimetic MDM2 mutants."
28196907
reach
"For example, USP7 (HAUSP) interacts with MDM2 to regulate the turnover of p53 together, and it is also able to increase the stability of MDM2 XREF_BIBR."
24714733
reach
"HAUSP preferentially forms a stable HAUSP and MDM2 complex even in the presence of excess p53."
16402859
reach
"It is likely that Mdm2 is the preferred substrate for HAUSP in unstressed cells, while genotoxic stress decreases HAUSP 's binding to Mdm2 and MdmX through ATM dependent phosphorylation, tilting the balance toward p53 stabilization."
20096447
biogrid
No evidence text available
16474402
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
"MDM2 acetylation and HAUSP interaction in U2OS cells declined 4 hours after treatment with ETO (XREF_FIG), supporting a model in which HAUSP associates with MDM2 possibly in an MDM2 acetylation dependent manner."
28196907
reach
"A previous study suggested that the interaction between HAUSP and Mdm2 is significantly decreased in response to DNA damage XREF_BIBR."
26238070
sparser
"USP7 can directly bind Mdm2 in vitro [ xref ]."
18687060
reach
"DAXX mediates the stabilizing effect of USP7 on MDM2 by promoting the binding of USP7 and MDM2."
25283148
reach
"The best known such example is provided by the association between USP7 and MDM2, which has rendered USP7 a prominent drug target, as a means to regulate levels of p53."
33507233
sparser
"USP7 protein (also known as HAUSP) plays a central role in Mdm2 regulation since self-ubiquitylation of Mdm2 promotes its own degradation ( xref ) that is rescued by formation of a complex between Mdm2 and USP7 proteins ( xref )."
22361354
reach
"Mdm2 seems to be the preferred substrate for USP7 in unstressed cells, and genotoxic stress decreases USP7 binding to Mdm2 through ATM dependent phosphorylation, shifting the balance toward p53 stabilization XREF_BIBR XREF_BIBR."
28233861
reach
"Compared to p53, the more extensive interactions between MDM2 and HAUSP provide a mechanistic explanation to our biochemical observation that MDM2 out competed excess p53 for binding to HAUSP."
16402859
biogrid
No evidence text available
26238070
reach
"Thus, our findings support the concept that USP7 through its interactions with SUV39H1 and MDM2 plays an important role in enforcing MDM2 mediated repression of p53 dependent transcription of its targ[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
sparser
"The proteasome has both ubiquitin ligases and DUBs that associate with it (Crosas et al., 2006) , and several DUB-ligase pairs interact directly, including BRCC36-BRCA1, BAP1-BRCA1, USP4-Ro52, USP7-MDM2, USP8-GRAIL, USP20-pVHL, USP33-pVHL and USP44-APC (Kee and Huibregtse, 2007; Marfany and Denuc, 2008; Ventii and Wilkinson, 2008) ."
19571111
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
"The knockdown of WDR79 not only abolished the effect of USP7 on Mdm2 and p53 but also decreased the binding of USP7 to Mdm2 and p53."
28406480
reach
"This finding led us to wonder whether HAUSP interaction and nuclear translocation of MDM2 are linked or separately regulated."
28196907
sparser
"HAUSP, a deubiquitinase, can bind to MDM2 [ xref ]."
29789718
sparser
"A minimal HAUSP-binding peptide derived from MDM2 efficiently displaced p53 from the p53–HAUSP complex in a competition assay and formed a stable HAUSP–MDM2 complex."
16402859
reach
"In addition, an interesting feedback loop exists in p53 regulation because USP7 also binds, deubiquitinates and stabilizes Mdm2 more potently under physiologic conditions [14, 15] and stabilizes p53 under genotoxic stress conditions [16, 17]."
32571254
reach
"This is because, in addition to deubiquitination of p53, USP7 also binds to MDM2."
25283148
sparser
"And because MDM2 consistently formed stable complexes with HAUSP despite the presence of ten times more p53 peptides, it was clear that MDM2 binds to the deubiquitylating enzyme with a higher affinity."
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
biogrid
No evidence text available
26971997
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
"31 However, upon DNA damage, ataxia telangiectasia mutated dependent phosphorylation of Mdm2 decreased the binding affinity between USP7 and Mdm2, tilting the balance towards p53 stabilization."
28406480
biogrid
No evidence text available
24462112
sparser
"HAUSP interaction with MDM2 was enhanced by Lys 182 acetylation ( xref )."
28196907
reach
"DAXX and HAUSP interact with MDM2 to form a tertiary complex, which reduces self ubiqitination of MDM2 [XREF_BIBR]."
25888903
sparser
"While the MDM2–USP7 interaction is best known in the context of p53 stability, it may also regulate p53 targets epigenetically through the SUV39H1 H3K9 methyltransferase [ xref ]."
30897496
reach
"One study showed that MDM2 interaction with the scaffold protein Daxx and deubiquiting enzyme HAUSP is stimulated by DNA damage, which promote p53 de-ubiquitination."
20081365
reach
"Dissociation of either of these proteins disrupts the stability of the Mdm2 and HAUSP complex and promotes Mdm2 auto-ubiquitination and degradation."
20404858
sparser
"Since USP7 forms a complex with Mdm2 and is required for Mdm2 stability, a knockout of USP7 in cells leads to Mdm2 self-ubiquitination and proteasomal degradation, which in turn results in Polη accumulation."
25435364
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
reach
"Analysis of the molecular basis of their differential binding revealed that MDM2 binds HAUSP with a much higher affinity, and suggests how HAUSP may regulate the critically important p53-MDM2 pathway."
20076526
hprd
No evidence text available
16845383
reach
"While the USP7-NTD was able to pull down SUV39H1 to a similar extent as full-length USP7, the USP7-CTD showed no detectable interaction, indicating that the NTD of USP7 is essential for protein comple[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
hprd
No evidence text available
16474402
sparser
"Acetylation at Lys 182 and Lys 185 in MDM2 by p300 promoted the interaction of MDM2 with the deubiquitinase HAUSP, thereby suppressing self-ubiquitination, as well as altered the conformation of MDM2, thereby enhancing its functional interaction with p53."
28196907
sparser
"Previous reports have indicated that MDM2 binds USP7 through interactions mediated by MDM2 aa 147–159 ( Sheng et al., 2006 ), while aa 200–262 are involved in MDM2 binding to SUV39H1 ( Fåhraeus and Ol[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
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
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
"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
"Several proteins have been reported to regulate the deubiquitination of p53 by affecting the interaction between USP7 and MDM2, or that between USP7 and p53."
25283148
reach
"However, since we are able to activate the catalytic domain with the addition of peptide, trans activation is certainly possible and could be employed as a regulatory mechanism of USP7 on some substra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27452404
sparser
"Concomitantly, RASSF1A binds to the DR associated protein DAXX, which results in the disruption of the interaction between MDM2 and HAUSP, resulting in MDM2 auto-ubiquitination and degradation inducing p53 stabilisation, which leads to cell cycle arrest and apoptosis."
31963420
sparser
"Alternatively they may coordinately regulate the stability of a third partner as exemplified by the association of MDM2 with USP7 (HAUSP), both regulators of p53 ( xref )."
23105109
sparser
"The affinities we measured for the USP7-MDM2 interaction are, however, consistent with MDM2 as a specific substrate of USP7, and the affinity of USP7 for MDM2 is similar to the binding affinity of UBL[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27452404
reach
"HAUSP, a deubiquitinase, can bind to MDM2 [21]."
29789718
sparser
"Although both the individual NTD and UBL domains have previously been reported to have some interaction with MDM2, it is clear from the SPR data that both the NTD and the UBL domains are necessary for[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27452404
biogrid
No evidence text available
17380154
reach
"Under normal conditions, USP7 preferentially interacts with HDM2 and prevents its degradation."
30807924
biogrid
No evidence text available
16943424
sparser
"Comparison of HAUSP Binding by MDM2 and by p53."
16402859
sparser
"Interestingly, the aforementioned USP7-MDM2 adaptor protein Daxx (Tang et al., 2006) is a major ND10 component (Everett et al., 2006), raising the question whether it also has an adaptor function for USP7 in this nuclear compartment."
17291557
sparser
"Because the KQKQ-MDM2 mutant bound HAUSP more strongly than did the wild-type MDM2 ( xref ), we hypothesized that acetylation within the NLS may promote HAUSP recruitment on the acidic domain."
28196907
biogrid
No evidence text available
16845383
sparser
"Daxx promotes the binding of MDM2 to HAUSP and thus increases MDM2 stability ( xref )."
25808808
sparser
"Under normal conditions, USP7 preferentially interacts with HDM2 and prevents its degradation ( xref )."
30807924
sparser
"However, under genotoxic stress conditions, binding of Mdm2 to USP7 is impaired as a result of ATM-mediated phosphorylation of Mdm2, shifting the balance towards stabilization of p53 [ xref , xref ]."
27844253
sparser
"Previous reports have indicated that MDM2 binds USP7 through interactions mediated by MDM2 aa147–159 ( xref ), while aa200–262 are involved in MDM2 binding to SUV39H1 ( xref )."
26971997
reach
"Our current structural studies identify differential features for HAUSP binding by MDM2 and by p53."
16402859
biogrid
No evidence text available
16474402
sparser
"USP7 (previously known as HAUSP), a deubiquitinase, interacts with MDM2 [ xref ]."
35008383
sparser
"MDM2 acetylation and HAUSP interaction in U2OS cells declined 4 hours after treatment with ETO ( xref ), supporting a model in which HAUSP associates with MDM2 possibly in an MDM2 acetylation–dependent manner."
28196907
reach
"Current evidence is that USP7 preferentially binds and deubiquitinates MDM2, thereby leading to increased degradation of p53, and consequent anti‐apoptotic functions."
20073038
reach
"We found that DNA damage induced HAUSP dissociation from MDM2 was largely diminished in SIRT1 depleted U2OS cells (XREF_FIG), supporting our model that MDM2 acetylation triggers a stable interaction of MDM2 and HAUSP."
28196907
sparser
"Intriguingly, HAUSP also binds and deubiquitinates Mdm2, thereby stabilizing Mdm2 and consequently destabilizing p53."
15865930
sparser
"We utilized a combination of biochemistry and structural biology to identify which domain of USP7 interacts with HdmX as well as to identify regions of HdmX that interact with USP7."
20713061
reach
"There are several examples of Ub ligase-DUB pairs where a DUB either regulates substrate ubiquitination or auto-ubiquitination of the Ub ligase, notably the Mdm2 and USP7 complex that regulates p53 stability and the DUB A20, which also harbors Ub ligase activity."
26997266
sparser
"Consistent with the previous reports of peptide binding to the USP7-NTD domain alone, we observed a weak interaction of full-length MDM2 with a USP7 construct containing NTD-USP7CD ( Figure 5 B )."
27452404
reach
"Since USP7 forms a complex with Mdm2 and is required for Mdm2 stability, a knockdown of USP7 employed in our experiments, leads to Mdm2 self ubiquitylation and proteasomal degradation (XREF_FIG, pathway 2)."
21138959
sparser
"DAXX mediates the stabilizing effect of USP7 on MDM2 by promoting the binding of USP7 and MDM2 (refs xref , xref )."
25283148
sparser
"A previous study suggested that the interaction between HAUSP and Mdm2 is significantly decreased in response to DNA damage xref ."
26238070
sparser
"Since USP7 forms a complex with Mdm2 and is required for Mdm2 stability ( xref , xref ), a knockdown of USP7 employed in our experiments, leads to Mdm2 self-ubiquitylation and proteasomal degradation ( xref , pathway 2)."
21138959
sparser
"Considering that USP7 binds to MDM2 via the TRAF domain instead of the catalytic core domain, berberine may block the USP7-MDM2 binding via interacting with the TRAF domain."
32300595
sparser
"We found that DNA damage–induced HAUSP dissociation from MDM2 was largely diminished in SIRT1 -depleted U2OS cells ( xref ), supporting our model that MDM2 acetylation triggers a stable interaction of MDM2 and HAUSP."
28196907
sparser
"Here, we show that HAUSP also interacts with Hdmx, resulting in its direct deubiquitination and stabilization."
15916963
reach
"Upon DNA damage the interaction between MDM2 and MDMX and USP7 decreases in an ATM dependent manner [XREF_BIBR]."
23151129
sparser
"To elucidate the mechanism by which MDM2 recognizes HAUSP, we sought to determine the structure of HAUSP TRAF-like domain bound to the minimal MDM2 fragment."
16402859
sparser
"Strategies can be devised to screen for specific inhibitors that target this interface, thus destabilizing HAUSP–MDM2 interactions."
16402859
hprd
No evidence text available
17936559
reach
"In unstressed cells, MDM2 interacts with DAXX and HAUSP and is stabilized in the MDM2, DAXX, and HAUSP complex, which leads to persistent ubiquitination and degradation of the tumor suppressor p53."
20935220
biogrid
No evidence text available
18566590
sparser
"The interaction between USP7 and Mdm2 is also enhanced by DAXX, which simultaneously binds both proteins and enhances the E3 ubiquitin ligase activity of Mdm2 towards p53 ( xref )."
32850836
reach
"Since USP7 forms a complex with Mdm2 and is required for Mdm2 stability, a knockout of USP7 in cells leads to Mdm2 self ubiquitination and proteasomal degradation, which in turn results in Poleta accumulation."
25435364
reach
"Later studies showed that HAUSP also forms a complex with Mdm2 and stabilizes Mdm2 by its de-ubiquitinase activity."
15865931
sparser
"Although USP7 can interact with both Mdm2 and p53 depending on the cellular context, USP7 preferentially forms a stable USP7-Mdm2 complex even in the presence of excess p53 [ xref ], indicating that USP7 predominantly functions to stabilize Mdm2."
33207738
sparser
"USP7 binds to and stabilizes MDM2 under stress-free conditions, resulting in p53 turnover in an MDM2-dependent manner ( xref )."
32300595
sparser
"The TRAF-like domain of HAUSP is regarded as the necessary region to bind to p53, and HAUSP interacts with MDM2 both in vivo and in vitro. xref , xref "
32532965
sparser
"HAUSP preferentially forms a stable HAUSP HDM2 complex, even in the presence of excess p53 [ xref ]."
23822887
reach
"Thus USP7 is able to stabilise both p53 and MDM2 [XREF_BIBR, XREF_BIBR, XREF_BIBR] and it has been hypothesised that EBNA1 can compete for the binding of USP7 to MDM2 and thereby affect the p53 pathway [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
29642420
reach
"Thus, we tested the nature of the interactions, if any, between USP7, SUV39H1 and MDM2."
26971997
sparser
"In addition, an interesting feedback loop exists in p53 regulation because USP7 also binds, deubiquitinates and stabilizes Mdm2 more potently under physiologic conditions [ xref , xref ] and stabilizes p53 under genotoxic stress conditions [ xref , xref ]."
32571254
sparser
"However, not only does depletion of HAUSP fail to decrease p53 levels, but it actually increases its levels since HAUSP binds to MDM2 and deubiquitinates it."
33906413
biogrid
No evidence text available
27452404
reach
"Intriguingly, HAUSP also binds and deubiquitinates Mdm2, thereby stabilizing Mdm2 and consequently destabilizing p53."
15865930
reach
"Therefore, a drug that prevents the formation of the Hdm2 and USP7 complex or inhibits its catalytic activity will benefit patients with cancer associated with a dysregulated Hdm2 protein."
25605410
biogrid
No evidence text available
16845383
biogrid
No evidence text available
20816748
sparser
"The recent biochemical and structural analyses have characterized four USP7-binding sites on MDM2, including 147 PSSS HLVSR PSTS 159 , 226 AGVS 229 , and 397 PSTS 400 , and Ser150 and Ser229 are critical for the MDM2-USP7 binding ( xref ; xref ; xref )."
32300595
hprd
No evidence text available
15916963
reach
"Second, MDM2 binding to HAUSP was found to be mutually exclusive with p53 binding to HAUSP."
16402859
sparser
"Studies have found that the binding of USP7 with MDM2 is much stronger than that with p53 [ xref ]."
| PMC
biogrid
No evidence text available
20713061
reach
"This result suggests that MDM2 binds to HAUSP with a higher affinity than does p53."
16402859
reach
"Other different residues of TRAF like domain also interact with MDM2, but not with p53, and vice versa, accounting for USP7 binding to MDM2 and p53 with the different affinities."
27893708
sparser
"Hu et al. followed the same approach to reveal the mechanism of HAUSP–MDM2 interactions, and identified a ten–amino acid fragment in MDM2 as key to HAUSP recognition."
20076526
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
sparser
"Later studies showed that HAUSP also forms a complex with Mdm2 and stabilizes Mdm2 by its de-ubiquitinase activity."
15865931
sparser
"However, we found that full-length USP7 binds MDM2 with nanomolar affinity ( Figure 5 A), although no direct interaction of USP7CD-UBL12345 with MDM2 was observed at concentrations of USP7 up to 500 n[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27452404
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
"A previous study suggested that Mdm2 mediates p53 stabilization through HAUSP expression, and Mdm2 and HAUSP can interact in a p53-independent manner xref ."
26238070
reach
"RASSF1A disrupts the interaction between Mdm2, DAXX, and HAUSP, thereby promoting Mdm2 ubiquitination, and consequently resulting in p53 stabilization."
19450511
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
reach
"In the presence of intact DAXX and HAUSP, the newly synthesized MDM2 could associate with DAXX and HAUSP again, leading to stabilization of MDM2 and new ubiquitination and degradation of p53."
20935220
sparser
"Previous studies have shown that MDM2 physically interacts with USP7 ( xref ), and also forms a complex with SUV39H1 ( xref )."
26971997
sparser
"Under identical experimental conditions, the MDM2 peptide bound to the HAUSP TRAF-like domain with a dissociation constant of 3 μM, 7-fold tighter than that of the p53 peptide ( xref D)."
16402859
biogrid
No evidence text available
26460617
reach
"On the contrary, compared to wild-type and the KRKR mutant, the KQKQ mutant exhibited increased interaction with HAUSP in both the nucleus and the cytoplasm, suggesting that nuclear translocation of MDM2 is not required for HAUSP interaction with MDM2, at least in this experimental setting (XREF_SUPPLEMENTARY)."
28196907
reach
"Expression of RASSF1, the product of which disrupts the interaction between MDM2 and HAUSP was significantly up-regulated in the clinical PNI samples."
27665737
reach
"However, we found that full-length USP7 binds MDM2 with nanomolar affinity, although no direct interaction of USP7CD-UBL12345 with MDM2 was observed at concentrations of USP7 up to 500 nM."
27452404
biogrid
No evidence text available
16402859
reach
"USP7 binds to p53 and mdm2, stabilizing the proteins."
34888589
sparser
"Thus USP7 is able to stabilise both p53 and MDM2 [ xref , xref , xref ] and it has been hypothesised that EBNA1 can compete for the binding of USP7 to MDM2 and thereby affect the p53 pathway [ xref , xref , xref ]."
29642420
biogrid
No evidence text available
28196907
sparser
"This result suggests that MDM2 binds to HAUSP with a higher affinity than does p53."
16402859
reach
"For example, a previous review from Pfoh et al. (2015) (190) proposed the development of a drug that would block interaction between MDM2 and USP7 in patients with cancer caused by hyperactivation of MDM2, thereby targeting MDM2 for degradation and stabilizing p53.By studying the DUBs and the pathways that are affected by their redox regulation, the upstream and downstream effectors that are deregulated due to DUB inactivity can be identified, and those can also become targets of therapeutic development."
34391779
reach
"Several proteins have been reported to regulate the deubiquitination of p53 by affecting the interaction between USP7 and MDM2, or that between USP7 and p53."
25283148
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
16402859
reach
"They find that, before stress signaling, USP7 binds and deubiquitylates MDM2, thus stabilizing MDM2 and promoting p53 degradation."
24507714
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
"Our current structural studies identify differential features for HAUSP binding by MDM2 and by p53."
16402859
biogrid
No evidence text available
16402859
reach
"As we expected, wild-type MDM2 and the KRKR MDM2 mutant, both of which dominantly express in the nucleus, interacted with HAUSP largely in the nucleus (XREF_SUPPLEMENTARY)."
28196907
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
reach
"In the normal state, HAUSP specifically binds to and deubiquitinates Mdm2, thereby stabilizing Mdm2 and subsequently inducing the proteasomal degradation of p53 through Mdm2 activity."
25695607
biogrid
No evidence text available
20713061
sparser
"This is because, in addition to deubiquitination of p53, USP7 also binds to MDM2."
25283148
biogrid
No evidence text available
26971997
reach
"Daxx promotes the binding of MDM2 to HAUSP and thus increases MDM2 stability."
25808808
reach
"However, under genotoxic stress conditions, binding of Mdm2 to USP7 is impaired as a result of ATM mediated phosphorylation of Mdm2, shifting the balance towards stabilization of p53 [XREF_BIBR, XREF_BIBR]."
27844253
reach
"Previous reports have indicated that MDM2 binds USP7 through interactions mediated by MDM2 aa147-159, while aa200-262 are involved in MDM2 binding to SUV39H1."
26971997
reach
"For example, by interacting with ubiquitin specific protease USP7 (as discussed below), it has been suggested that EBNA1 could interfere with p53 's or MDM2 's own binding to USP7, leading in particular to lower levels of the p53 transcriptional activator, thereby promoting cell survival in response to cellular stress [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
29642420
sparser
"A proposed mechanism for the dissociation of Mdm2 from HAUSP involves ATM phosphorylation of Daxx (death domain-associated protein 6) triggering its dissociation from Mdm2, and relieving Daxx mediated promotion of Mdm2-HAUSP interaction ( xref , xref )."
28690977
reach
"However, EBNA1 binds this pocket with higher affinity than either p53 or Mdm2 and therefore interferes with p53 or Mdm2 binding to USP7 at least in vitro [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
23170171
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
trips
"Here, we show that HAUSP also interacts with Hdmx, resulting in its direct deubiquitination and stabilization."
15916963
sparser
"Compared to p53, the more extensive interactions between MDM2 and HAUSP provide a mechanistic explanation to our biochemical observation that MDM2 out-competed excess p53 for binding to HAUSP."
16402859
sparser
"Previous studies have shown that MDM2 physically interacts with USP7 ( Sheng et al., 2006 ) and also forms a complex with SUV39H1 ( Fåhraeus and Olivares-Illana, 2014 )."
26971997
biogrid
No evidence text available
17936559
sparser
"To this end, we conducted cell fractionation assays to determine the subcellular localization where HAUSP interacts with MDM2 in 293T cells."
28196907
sparser
"In the structure of the HAUSP–MDM2 fusion protein, the MDM2 peptide (residues 223–230) is bound to the shallow surface groove on one side of the β-sandwich in the TRAF-like domain, the same site where p53 binds."
16402859
sparser
"Analysis of the molecular basis of their differential binding revealed that MDM2 binds HAUSP with a much higher affinity, and suggests how HAUSP may regulate the critically important p53–MDM2 pathway. xref "
20076526
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
biogrid
No evidence text available
16474402
reach
"Previous studies have shown that MDM2 physically interacts with USP7, and also forms a complex with SUV39H1."
26971997
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