IndraLab

Statements

USP7 affects MDM2
2 24 4 1 | 10 2 239 166
USP7 binds MDM2.
24 4 | 1 111 166
USP7 binds MDM2. 10 / 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
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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
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"USP7 can directly bind Mdm2 in vitro [XREF_BIBR]."
18687060
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"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
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"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
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"Expression of RASSF1 , the product of which disrupts the interaction between MDM2 and HAUSP was significantly up-regulated in the clinical PNI samples."
27665737
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"USP7 can bind directly to Mdm2 or p53 in a mutually exclusive manner."
26460617
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"We then employed co-immunoprecipitation to identify possible changes in the binding of USP7 to Mdm2 and p53."
28406480
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"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
TP53 binds USP7 and MDM2. 10 / 51
| 13 38
sparser
"In addition, USP7 can interact indirectly with p53, using Mdm2 as a bridge, resulting in the formation of USP7-Mdm2-p53 complexes."
26460617
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"The HAUSP, p53, and Mdm2 complex and p53-nucleolin interplay in DNA damage have been identified XREF_BIBR XREF_BIBR XREF_BIBR; however, the molecular relation between these two findings was poorly understood."
26238070
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"Taken together, the activation of USP7-MDM2-p53 interaction can promote the occurrence and development of tumors."
31114498
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"P53, as a tumour-suppressor, exerts an essential role in signalling associated with the control of cell survival and aberrant p53 signalling results in unchecked cell growth and the initiation of cancer.USP7 interacts with a range of protein targets in the p53 pathway (p53, MDMX, MDM2)39 and MDM2 plays a key role in p53 stabilization by increasing the ubiquitination process.39 USP7 deubiquitinates MDM2 and its functional regulator MdmX and stabilizes p53.39 USP7 apparently has 2 independent p53 regulatory functions, stabilizing p53 through deubiquitylation and regulating the sequence-specific DNA binding of p53.40 Within the USP7, MDM2 and p53 complex, p53 and the MDM2 have been shown to bind USP7 through the TRAF domain.39 Under normal conditions, USP7 prefers MDM2 as a substrate rather than p53 and MDM2 has a higher binding affinity for USP7 compared to p53.41 Reduction of USP7 expression levels leads to p53 stabilisation, and destabilization of MDM2."
35005106
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"The authors find that genotoxic stress induces a shift in complex formation from a p53, MDM2, and USP7 complex to p53/GMPS/USP7."
24507714
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"Binding of HAUSP to either p53 or MDM2 leads to their de-ubiquitination, and binding to MDM2 leads to p53 destabilization due to increased MDM2 stability [ xref ]."
19538162
sparser
"USP7 can bind directly to Mdm2 or p53 in a mutually exclusive manner."
26460617
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
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"However, the linkage between the DNA damage response machinery and the HAUSP, p53, and Mdm2 complex in DNA damaged cells still remain unresolved."
26238070
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"Taken together, this study reveals a new component of the HAUSP, p53, and Mdm2 complex that governs dynamic cellular responses to DNA damage."
26238070
USP7 binds DAXX and MDM2. 10 / 45
| 18 27
sparser
"RASSF1A disrupts the interaction between Mdm2, DAXX, and HAUSP, thereby promoting Mdm2 ubiquitination, and consequently resulting in p53 stabilization."
19450511
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"Song et al. [20] recently showed that, in response to DNA damage, RASSF1A promotes the disruption of the MDM2, DAXX, and HAUSP complex, which results in MDM2 self ubiquitination, p53 stabilization, an[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19962312
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"RASSF1A has been reported to control the assembly of the USP7, DAXX, and MDM2 complex by blocking interactions among MDM2, DAXX and USP7, and by promoting the ubiquitination of MDM2, resulting in stabilization of p53."
25283148
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"XREF_BIBR, XREF_BIBR Clinical trials of Trisenox (arsenic trioxide), which is used for treatment of acute promyelocytic leukemia (APL), disrupts the MDM2, DAXX, and HAUSP complex (reported at AACR 2016)."
29967688
sparser
"In our previous studies, we have found that Daxx forms a complex with the E3 ubiquitin ligase Mdm2 and the de-ubiquitinase Hausp."
20153724
sparser
"In unstressed cells, MDM2 interacts with DAXX and HAUSP and is stabilized in the MDM2-DAXX-HAUSP complex, which leads to persistent ubiquitination and degradation of the tumor suppressor p53."
20935220
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"It has been reported that RASSF1A negatively regulates MDM2 by disrupting the MDM2, DAXX, and HAUSP complex and inducing the self ubiquitination of MDM2 [XREF_BIBR]."
29179447
sparser
"In further studies, we demonstrated that berberine uniquely downregulated the expression of DAXX in a dose- and time-dependent manner, and because of that DAXX absence in berberine-treated cells, no new formation of the MDM2-DAXX-HAUSP complex was possible, so the p53-induced newly-synthesized MDM2 constitutively underwent self-ubiquitination and degradation."
20935220
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"In further studies, we demonstrated that berberine uniquely downregulated the expression of DAXX in a dose- and time dependent manner, and because of that DAXX absence in berberine treated cells, no new formation of the MDM2, DAXX, and HAUSP complex was possible, so the p53 induced newly synthesized MDM2 constitutively underwent self ubiquitination and degradation."
20935220
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"We investigated whether berberine, like doxorubicin, induces a similar disruption of the MDM2, DAXX, and HAUSP complex."
20935220
SUV39H1 binds USP7 and MDM2. 7 / 7
| 3 4
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"Whether this protection occurs on p53 target promoters alone and/or elsewhere within the cell as well as the physiological significance of these interactions in a p53 null context remain to be elucida[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
sparser
"USP7 forms a trimeric protein complex with SUV39H1 and MDM2."
26971997
sparser
"Collectively, these results indicate that shared physical interactions of USP7 and SUV39H1 with MDM2 are required either for USP7 to deubiquitinate SUV39H1 or for MDM2 to ubiquitinate SUV39H1, both re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
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"Our present findings as well as data available from previous reports indicate that ' basal ' levels of mostly transcriptionally inactive p53 enable the recruitment of the USP7, MDM2, and SUV39H1 complex to p53 REs via p53-MDM2 interaction, placing the H3K9me3 repressive mark and maintaining low basal transcription activity of p53 target genes (XREF_FIG)."
26971997
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"Our present studies demonstrate that USP7, SUV39H1 and MDM2 exist in a trimeric complex and that the USP7, MDM2, and SUV39H1 complex keeps MDM2 inactive under basal conditions."
26971997
sparser
"Collectively, these results indicate that shared physical interactions of USP7 and SUV39H1 with MDM2 are required for either for USP7 to deubiquitinate SUV39H1 or for MDM2 to ubiquitinate SUV39H1; both resulting in enhanced SUV39H1 stability."
26971997
sparser
"Mechanistically, USP7 forms a trimeric complex with MDM2 and SUV39H1, independent of DNA, and modulates MDM2-dependent SUV39H1 ubiquitination."
26971997
USP7 binds MDM2 and MDM4. 4 / 4
| 4
sparser
"Phosphorylation defective mutants of MdmX (single-, double-, or triple- phosphorylation mutants) have reduced binding ability with Mdm2 but have enhanced binding activity with USP7 in the DNA damage stressed cells ( xref ), suggesting that DNA damage-induced phosphorylation of MdmX may influence binding of MdmX to Mdm2 and USP7."
19808970
sparser
"ATM- and PPM1G-dependent dephosphorylation of serine 18 in the N-terminus of Hausp has been reported to drive the DNA damage dependent disruption of Hausp interaction with Mdm2 and MdmX ( xref )."
25756610
sparser
"Under non-stressed conditions, for example, the MDM2-MDMX complex also binds to the deubiquitinating protein HAUSP, which stabilizes both MDM2 and MDMX ( xref , xref )."
23002429
sparser
"USP7 directly interacts with MDM2 and MDMX, regardless of p53 status."
32300595
TRAF binds USP7 and MDM2. 2 / 2
| 2
sparser
"Conversely, the TRAF domain and C-terminal (amino acids 801–1050) of USP7 can interact with MDM2 and increase its stability by removing ubiquitin from MDM2, an E3 ligase of p53, preventing its degradation [ xref ]."
33805973
sparser
"On the other hand, TRAF domain and C-terminal (amino acids 801–1050) of USP7 can interact with MDM2 to increase its stability by erasing the ubiquitin on MDM2, an E3 ligase of p53 ( xref ), and protect it from proteasome degradation."
31114498
TP53 binds USP7, WRAP53, and MDM2. 2 / 2
| 2
sparser
"In this study, we report a new molecular process in which WDR79 interacts with USP7 to modulate the stability of Mdm2 and p53, which promotes the proliferation of NSCLC cells."
28406480
sparser
"Taken together, our findings reveal a novel role of WDR79 in the proliferation of NSCLC cells and could pinpoint a new mechanism by which WDR79 and USP7 functionally interact to modulate the Mdm2-p53 pathway."
28406480
TP53 binds USP7, DAXX, and MDM2. 2 / 2
| 1 1
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"The most significant binding partners identified to interact with the C1 domain are the TNF-R1 and TRAIL-R1 -- Modulator of Apoptosis-1 (MOAP-1) complexes and the MDM2, DAXX, HAUSP, and p53 complex [XREF_BIBR, XREF_BIBR] (XREF_FIG)."
22577550
sparser
"Although the molecular mechanism for the interactions of DAXX, HAUSP, Mdm2, and p53 underlying this regulatory pathway are largely unknown, an important clue is provided by our observation that, at le[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21134643
TP53 binds USP7, ELP2, and MDM2. 2 / 2
| 2
sparser
"Considering that the effect of STIP on Mdm2 or p53 was independent of each other, we hypothesize that STIP may associate with the USP7-Mdm2 or USP7-p53 complexes."
26460617
sparser
"These data indicated that STIP may simultaneously bind to USP7 and either Mdm2 or p53, mediating the assembly of ternary STIP-USP7-Mdm2 and STIP-USP7-p53 complexes, respectively."
26460617
TP53 binds USP7, MDM2, and NCL. 2 / 2
| 2
sparser
"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
"Moreover, p53 also could not interact with HAUSP and nucleolin in Mdm2-depleted cells ( xref )."
26238070
USP7 binds MDM2 and NCL. 2 / 2
| 2
sparser
"We also observed a HAUSP-nucleolin interaction in Mdm2-depleted cells under IR treatment."
26238070
sparser
"In contrary, knockdown of p53 did not affect HAUSP-nucleolin and HAUSP-Mdm2 interaction ( xref )."
26238070
TP53 binds USP7, MDM2, and MDM4. 1 / 1
| 1
sparser
"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
USP7 binds BAG6 and MDM2. 1 / 1
| 1
sparser
"We next wished to deduce whether Mdm2, Bat3 and HAUSP could also form a three-protein complex."
31647545
Ubiquitin binds TP53, USP7, and MDM2. 1 / 1
| 1
sparser
"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
USP7 binds MDM2 and 293T. 1 / 1
| 1
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"To this end, we conducted cell fractionation assays to determine the subcellular localization where HAUSP interacts with MDM2 in 293T cells."
28196907
USP2 binds USP7 and MDM2. 1 / 1
| 1
sparser
"USP10 is also associated with regulation of p53 localization and stability, however, unlike USP2 and USP7, it does not interact with MDM2 [ xref ]."
25972356
Ubiquitin binds TP53, USP7, MDM2, and TraF. 1 / 1
| 1
sparser
"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 – xref ]."
26460617
USP7 binds LIF, MDM2, and MDM4. 1 / 1
| 1
sparser
"Using the same cohort, we expanded the analysis to other TP53 signaling network genes [ xref ], and in contrast with previous findings, our results demonstrated no association of MDM2 , MDM4 , USP7 , and LIF polymorphisms with endometriosis-related infertility or IVF failure patients."
24427778
USP7 binds MDM2 and ATM. 1 / 1
| 1
sparser
"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 xref ."
28233861
TP53 binds USP7, CDKN1A, and MDM2. 1 / 1
| 1
sparser
"In addition to the altered levels of HDM2, p53 and p21 associated with its use, P22077 treatment also caused reduced levels of DNA damage proteins DDB1, RBX1, DCAF7 and DCAF11, all of which are subunits of E3 ligases, indicating a previously unknown functional link between USP7 and enzymes involved in DNA repair [ xref ]."
23822887
USP7 binds mutated MDM2. 1 / 1
| 1
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"Because the KQKQ MDM2 mutant bound HAUSP more strongly than did the wild-type MDM2 (XREF_FIG), we hypothesized that acetylation within the NLS may promote HAUSP recruitment on the acidic domain."
28196907
GST binds TP53, USP7, MDM2, and NCL. 1 / 1
| 1
sparser
"As expected, purified GST-p53 protein could bind Mdm2, nucleolin, and HAUSP ( xref , upper panel)."
26238070
USP10 binds USP7 and MDM2. 1 / 1
| 1
sparser
"Unlike HAUSP, USP10 did not interact with Mdm2 ( xref )."
20096447
USP7 binds DAXX, MDM2, and RASSF1. 1 / 1
| 1
sparser
"Song MS, et al. reported that RASSF1A could directly interact with Mdm2, HAUSP, and Daxx protein [ xref ]."
30615685
USP7 deubiquitinates MDM2.
1 1 | 1 58
USP7 deubiquitinates MDM2. 10 / 61
1 1 | 1 58
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"Thus USP7 would be posited to have opposing effects depending on whether it predominantly deubiquitinates and rescues p53 or MDM2."
20073038
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"USP7 deubiquitinates both p53 and MDM2, one of the ubiquitin ligases that ubiquitylates p53, thereby stabilizing both proteins [XREF_BIBR, XREF_BIBR]."
29142505
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"USP7 preferentially deubiquitylates the E3 ligase HDM2 and its binding partner HDMX as well as their substrate p53 (Brooks et al., 2007; Cummins and Vogelstein, 2004; Li et al., 2002, 2004; Meulmeeste[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22118674
ubibrowser
"Review"
28801249
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"USP7 deubiquitinates Mdm2 and p53, and its overexpression causes Mdm2 and p53 stabilization."
26460617
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"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
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"XREF_BIBR - XREF_BIBR USP7 deubiquitinates and stabilizes not only p53, but also Mdm2, the primary E3 ubiquitin ligase of p53 XREF_BIBR, XREF_BIBR Given that both p53 and Mdm2 are known regulators of the steady-level of Poleta, we speculated that changes in cellular USP7 levels may also modulate Poleta level."
25435364
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"HAUSP not only deubiquitinates p53, but also Mdm2."
19450511
reach
"USP7, also known as the hepes simplex virus associated ubiquitin specific protease (HAUSP), deubiquitinates both mdm2 and p53, and plays an important role in regulating the level and activity of p53."
20816748
reach
"USP7 preferentially deubiquitylates the E3 ligase HDM2 and its binding partner HDMX, resulting in the destabilisation of p53 and the repression of p53 transactivation activity."
22088887
USP7 activates MDM2.
1 | 9 40
USP7 activates MDM2. 10 / 53
1 | 9 38
eidos
"The stabilized USP7 / HAUSP can enhance Mdm2 and decrease p53 protein expression ."
| PMC
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"USP7 inhibition promotes the degradation of MDM2 and MDMX, activates the p53 signaling, and causes cell cycle arrest and apoptosis, making USP7 a potential target for cancer therapy."
32300595
eidos
"Our study suggests that USP7 up-regulates MDM2 , which facilitates FoxO4 ubiquitinated degradation , and subsequently increases the expression of CyclinD1 to mediate PDGF-induced PASMCs proliferation ."
34552711
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"This study provides an example of an ubiquitin ligase (Mdm2) that is directly regulated by a deubiquitinase (HAUSP) and also reveals a dynamic role of HAUSP in the p53-Mdm2 pathway."
15053880
reach
"This interference is first evidenced by the response to oxidative DNA damage and modulation of DNA accessibility to base excision repair (BER) machinery, which is an indirect effect due to HAUSP mediated MDM2 regulation."
29967688
eidos
"Importantly , around the same time , the Gu lab , who initially identified USP7 , similarly reported that USP7 loss destabilizes Mdm2 , and this is concomitant with an accumulation of p53 and an induction of cell cycle arrest in G1 through subsequent upregulation of the CKI p2175 ."
32201366
reach
"Examples of MDM2 regulators are : ARF4 that may dampen the p53 pathway by releasing MDM2; HAUSP that targets MDM2 resulting in its stabilization and negative regulation of the p53 pathway; and WIP1, a phosphatase that dephosphorylates MDM2 preventing prolonged p53-pathway activation [XREF_BIBR]."
27916892
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"Accumulated studies have suggested that USP7, through modulating the MDM2/MDMX-p53 pathway, is a promising target for cancer treatment; however, little is known about the function of USP7 in p53-deficient tumors."
34580281
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"Therefore, inhibition of USP7 should cause degradation of MDM2, which, in turn, should increase the stability of p53 and suppress cancer progression in tumors with wild-type p53 (XREF_FIG)."
30913483
reach
"USP10 directly interacts with p53 to remove Ub, while USP7 seems to preferentially target MDM2 [2,7,8]."
28284458
USP7 bound to WRAP53 activates MDM2. 1 / 1
| 1
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"XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR In this study, we report a new molecular process in which WDR79 interacts with USP7 to modulate the stability of Mdm2 and p53, which promotes the proliferation of NSCLC cells."
28406480
USP7 bound to MDM2 activates MDM2. 1 / 1
| 1
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"Daxx promotes the binding of MDM2 to HAUSP and thus increases MDM2 stability."
25808808
USP7 inhibits MDM2.
| 1 15
USP7 inhibits MDM2. 10 / 17
| 1 14
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"USP7 impairs the balance of the p53/MDM2 axis resulting in the proteasomal degradation of the p53 tumor suppressor, a process that can be reversed by small-molecule inhibitors of USP7."
36428632
eidos
"In the control cells , USP7 inhibition significantly upregulated the HDAC1 , PSMD10 , MDM4 , and MDM2 genes after 24 h , but downregulated these genes after four days ."
36624687
reach
"Partial reductions in HAUSP levels lead to destabilization of p53, whereas more complete reductions may cause MDM2 destabilization and p53 accumulation."
32532965
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"25 USP7 deficiency in mouse embryonic fibroblasts (MEFs) greatly reduces the half-life of MDM2 and activates p53."
24136231
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"Here, we report that in response to DNA damage USP7 is downregulated by the ATM dependent protein phosphatase PPM1G, thus downregulating Mdm2 and activating the p53 response."
22361354
reach
"USP7 also negatively regulates the stability of MDM2."
28067843
reach
"As USP7 participates in regulating the P53-murine double minute-2 (MDM2) axis XREF_BIBR, abrogation of USP7 is considered to inactivate MDM2 and subsequently reactivate P53, leading to cell cycle arrest and apoptosis XREF_BIBR."
33777676
reach
"Interestingly, severe ablation of USP7 expression diminished Mdm2 but increased Poleta (XREF_FIG)."
25435364
reach
"XREF_BIBR HAUSP antagonizes the action of MDM2 on P53."
25610759
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"In the control cells, USP7 inhibition significantly upregulated the HDAC1, PSMD10, MDM4, and MDM2 genes after 24 h, but downregulated these genes after four days."
36624687
Modified USP7 inhibits MDM2. 1 / 1
| 1
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"Overexpression of USP7 partially, but significantly attenuated ursolic acid induced cell death as well as downregulation of MDM2, UHRF1 and DNMT1."
29168472
USP7 increases the amount of MDM2.
| 9
USP7 increases the amount of MDM2. 8 / 8
| 8
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"As shown in XREF_FIG, knockdown of USP7 reduced the levels of Mdm2 and p53, a result consistent with that of a previous study."
28406480
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"Inhibition of USP7 decreases Mdm2 levels resulting in a corresponding increase in p53, inducing apoptosis."
30528168
reach
"As shown by the Gu group, partial reduction of USP7 levels in several human cell lines promotes decreased levels of both MDM2 and p53, yet total abolition of USP7 stabilizes p53 levels by decreasing MDM2 [117, 118]."
24239534
reach
"Thus, HAUSP-mediated de-ubiquitination can bring about increased levels of MDM2 that then accelerate p53 degradation to directly reduce the level of p53."
32532965
reach
"Moreover, while the levels of Mdm2 were enhanced by USP7 co-transfection, Mdm2 mediated Poleta degradation was indeed strongly rescued by USP7 overexpression (XREF_FIG)."
25435364
reach
"USP7 silencing by siRNA reduces chromatin accessibility and repair by modulating Mdm2 levels."
21138959
reach
"USP7 (ubiquitin specific protease 7), which deubiquitinates HDM2, can lead to increased levels of HDM2 and decreased levels of p53."
22649774
reach
"In fact, we found that HAUSP silencing in SAMe-D cells induced a decrease in Mdm2 levels (XREF_FIG), the major substrate stabilized by HAUSP, and an increase in nuclear localization of p53 after UVC treatment (XREF_FIG left panel)."
20815019
Modified USP7 increases the amount of MDM2. 1 / 1
| 1
reach
"As shown by the Gu group, partial reduction of USP7 levels in several human cell lines promotes decreased levels of both MDM2 and p53, yet total abolition of USP7 stabilizes p53 levels by decreasing MDM2 [117, 118]."
24239534
USP7 decreases the amount of MDM2.
| 3
USP7 decreases the amount of MDM2. 3 / 7
| 3
reach
"UbV.7.2 inhibited USP7 in cancer cells, and consequently, caused dramatic reductions of MDM2 levels and induction of apoptosis, in synergy with cisplatin, suggesting that UbVs could be used as enhancers of chemotherapeutic drugs."
30851297
reach
"Indeed, downregulation of USP10 did not affect Mdm2 levels in p53 deficient cells (XREF_FIG and XREF_SUPPLEMENTARY), while downregulation of HAUSP still decreased Mdm2 levels in p53 deficient cells."
20096447
reach
"UbV.7.2 inhibited USP7 in cancer cells, and consequently, caused dramatic reductions of MDM2 levels and induction of apoptosis, in synergy with cisplatin, suggesting that UbVs could be used as enhancers of chemotherapeutic drugs (W. Zhang, Sartori, et al., 2017)."
30851297
USP7 ubiquitinates MDM2.
| 3
USP7 leads to the ubiquitination of MDM2. 1 / 3
| 1
reach
"Phosphorylation of Mdm2 and Mdmx after DNA damage induces HAUSP dissociation, which increases Mdm2 auto-ubiquitination, trans-ubiquitination of Mdmx, and accelerates the turnover of both."
19147532
Modified USP7 leads to the ubiquitination of MDM2. 2 / 2
| 2
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"Disruption of the USP7 gene is also lethal to p53 wt cells, as loss of USP7 expression enhances the auto-ubiquitination of MDM2 leading to its degradation, resulting in p53 stabilization and apoptosis."
26971997
reach
"Disruption of the USP7 gene is also lethal to p53 wild-type (WT) cells, as loss of USP7 expression enhances the auto-ubiquitination of MDM2 leading to its degradation, resulting in p53 stabilization a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
MDM2 affects USP7
24 4 | 1 123 166
MDM2 binds USP7.
24 4 | 1 111 166
USP7 binds MDM2. 10 / 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
TP53 binds USP7 and MDM2. 10 / 51
| 13 38
sparser
"In addition, USP7 can interact indirectly with p53, using Mdm2 as a bridge, resulting in the formation of USP7-Mdm2-p53 complexes."
26460617
reach
"The HAUSP, p53, and Mdm2 complex and p53-nucleolin interplay in DNA damage have been identified XREF_BIBR XREF_BIBR XREF_BIBR; however, the molecular relation between these two findings was poorly understood."
26238070
sparser
"Taken together, the activation of USP7-MDM2-p53 interaction can promote the occurrence and development of tumors."
31114498
reach
"P53, as a tumour-suppressor, exerts an essential role in signalling associated with the control of cell survival and aberrant p53 signalling results in unchecked cell growth and the initiation of cancer.USP7 interacts with a range of protein targets in the p53 pathway (p53, MDMX, MDM2)39 and MDM2 plays a key role in p53 stabilization by increasing the ubiquitination process.39 USP7 deubiquitinates MDM2 and its functional regulator MdmX and stabilizes p53.39 USP7 apparently has 2 independent p53 regulatory functions, stabilizing p53 through deubiquitylation and regulating the sequence-specific DNA binding of p53.40 Within the USP7, MDM2 and p53 complex, p53 and the MDM2 have been shown to bind USP7 through the TRAF domain.39 Under normal conditions, USP7 prefers MDM2 as a substrate rather than p53 and MDM2 has a higher binding affinity for USP7 compared to p53.41 Reduction of USP7 expression levels leads to p53 stabilisation, and destabilization of MDM2."
35005106
reach
"The authors find that genotoxic stress induces a shift in complex formation from a p53, MDM2, and USP7 complex to p53/GMPS/USP7."
24507714
sparser
"Binding of HAUSP to either p53 or MDM2 leads to their de-ubiquitination, and binding to MDM2 leads to p53 destabilization due to increased MDM2 stability [ xref ]."
19538162
sparser
"USP7 can bind directly to Mdm2 or p53 in a mutually exclusive manner."
26460617
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
reach
"However, the linkage between the DNA damage response machinery and the HAUSP, p53, and Mdm2 complex in DNA damaged cells still remain unresolved."
26238070
reach
"Taken together, this study reveals a new component of the HAUSP, p53, and Mdm2 complex that governs dynamic cellular responses to DNA damage."
26238070
USP7 binds DAXX and MDM2. 10 / 45
| 18 27
sparser
"RASSF1A disrupts the interaction between Mdm2, DAXX, and HAUSP, thereby promoting Mdm2 ubiquitination, and consequently resulting in p53 stabilization."
19450511
reach
"Song et al. [20] recently showed that, in response to DNA damage, RASSF1A promotes the disruption of the MDM2, DAXX, and HAUSP complex, which results in MDM2 self ubiquitination, p53 stabilization, an[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19962312
reach
"RASSF1A has been reported to control the assembly of the USP7, DAXX, and MDM2 complex by blocking interactions among MDM2, DAXX and USP7, and by promoting the ubiquitination of MDM2, resulting in stabilization of p53."
25283148
reach
"XREF_BIBR, XREF_BIBR Clinical trials of Trisenox (arsenic trioxide), which is used for treatment of acute promyelocytic leukemia (APL), disrupts the MDM2, DAXX, and HAUSP complex (reported at AACR 2016)."
29967688
sparser
"In our previous studies, we have found that Daxx forms a complex with the E3 ubiquitin ligase Mdm2 and the de-ubiquitinase Hausp."
20153724
sparser
"In unstressed cells, MDM2 interacts with DAXX and HAUSP and is stabilized in the MDM2-DAXX-HAUSP complex, which leads to persistent ubiquitination and degradation of the tumor suppressor p53."
20935220
reach
"It has been reported that RASSF1A negatively regulates MDM2 by disrupting the MDM2, DAXX, and HAUSP complex and inducing the self ubiquitination of MDM2 [XREF_BIBR]."
29179447
sparser
"In further studies, we demonstrated that berberine uniquely downregulated the expression of DAXX in a dose- and time-dependent manner, and because of that DAXX absence in berberine-treated cells, no new formation of the MDM2-DAXX-HAUSP complex was possible, so the p53-induced newly-synthesized MDM2 constitutively underwent self-ubiquitination and degradation."
20935220
reach
"In further studies, we demonstrated that berberine uniquely downregulated the expression of DAXX in a dose- and time dependent manner, and because of that DAXX absence in berberine treated cells, no new formation of the MDM2, DAXX, and HAUSP complex was possible, so the p53 induced newly synthesized MDM2 constitutively underwent self ubiquitination and degradation."
20935220
reach
"We investigated whether berberine, like doxorubicin, induces a similar disruption of the MDM2, DAXX, and HAUSP complex."
20935220
SUV39H1 binds USP7 and MDM2. 7 / 7
| 3 4
reach
"Whether this protection occurs on p53 target promoters alone and/or elsewhere within the cell as well as the physiological significance of these interactions in a p53 null context remain to be elucida[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
sparser
"USP7 forms a trimeric protein complex with SUV39H1 and MDM2."
26971997
sparser
"Collectively, these results indicate that shared physical interactions of USP7 and SUV39H1 with MDM2 are required either for USP7 to deubiquitinate SUV39H1 or for MDM2 to ubiquitinate SUV39H1, both re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26971997
reach
"Our present findings as well as data available from previous reports indicate that ' basal ' levels of mostly transcriptionally inactive p53 enable the recruitment of the USP7, MDM2, and SUV39H1 complex to p53 REs via p53-MDM2 interaction, placing the H3K9me3 repressive mark and maintaining low basal transcription activity of p53 target genes (XREF_FIG)."
26971997
reach
"Our present studies demonstrate that USP7, SUV39H1 and MDM2 exist in a trimeric complex and that the USP7, MDM2, and SUV39H1 complex keeps MDM2 inactive under basal conditions."
26971997
sparser
"Collectively, these results indicate that shared physical interactions of USP7 and SUV39H1 with MDM2 are required for either for USP7 to deubiquitinate SUV39H1 or for MDM2 to ubiquitinate SUV39H1; both resulting in enhanced SUV39H1 stability."
26971997
sparser
"Mechanistically, USP7 forms a trimeric complex with MDM2 and SUV39H1, independent of DNA, and modulates MDM2-dependent SUV39H1 ubiquitination."
26971997
USP7 binds MDM2 and MDM4. 4 / 4
| 4
sparser
"Phosphorylation defective mutants of MdmX (single-, double-, or triple- phosphorylation mutants) have reduced binding ability with Mdm2 but have enhanced binding activity with USP7 in the DNA damage stressed cells ( xref ), suggesting that DNA damage-induced phosphorylation of MdmX may influence binding of MdmX to Mdm2 and USP7."
19808970
sparser
"ATM- and PPM1G-dependent dephosphorylation of serine 18 in the N-terminus of Hausp has been reported to drive the DNA damage dependent disruption of Hausp interaction with Mdm2 and MdmX ( xref )."
25756610
sparser
"Under non-stressed conditions, for example, the MDM2-MDMX complex also binds to the deubiquitinating protein HAUSP, which stabilizes both MDM2 and MDMX ( xref , xref )."
23002429
sparser
"USP7 directly interacts with MDM2 and MDMX, regardless of p53 status."
32300595
TRAF binds USP7 and MDM2. 2 / 2
| 2
sparser
"Conversely, the TRAF domain and C-terminal (amino acids 801–1050) of USP7 can interact with MDM2 and increase its stability by removing ubiquitin from MDM2, an E3 ligase of p53, preventing its degradation [ xref ]."
33805973
sparser
"On the other hand, TRAF domain and C-terminal (amino acids 801–1050) of USP7 can interact with MDM2 to increase its stability by erasing the ubiquitin on MDM2, an E3 ligase of p53 ( xref ), and protect it from proteasome degradation."
31114498
TP53 binds USP7, WRAP53, and MDM2. 2 / 2
| 2
sparser
"In this study, we report a new molecular process in which WDR79 interacts with USP7 to modulate the stability of Mdm2 and p53, which promotes the proliferation of NSCLC cells."
28406480
sparser
"Taken together, our findings reveal a novel role of WDR79 in the proliferation of NSCLC cells and could pinpoint a new mechanism by which WDR79 and USP7 functionally interact to modulate the Mdm2-p53 pathway."
28406480
TP53 binds USP7, DAXX, and MDM2. 2 / 2
| 1 1
reach
"The most significant binding partners identified to interact with the C1 domain are the TNF-R1 and TRAIL-R1 -- Modulator of Apoptosis-1 (MOAP-1) complexes and the MDM2, DAXX, HAUSP, and p53 complex [XREF_BIBR, XREF_BIBR] (XREF_FIG)."
22577550
sparser
"Although the molecular mechanism for the interactions of DAXX, HAUSP, Mdm2, and p53 underlying this regulatory pathway are largely unknown, an important clue is provided by our observation that, at le[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21134643
TP53 binds USP7, ELP2, and MDM2. 2 / 2
| 2
sparser
"Considering that the effect of STIP on Mdm2 or p53 was independent of each other, we hypothesize that STIP may associate with the USP7-Mdm2 or USP7-p53 complexes."
26460617
sparser
"These data indicated that STIP may simultaneously bind to USP7 and either Mdm2 or p53, mediating the assembly of ternary STIP-USP7-Mdm2 and STIP-USP7-p53 complexes, respectively."
26460617
TP53 binds USP7, MDM2, and NCL. 2 / 2
| 2
sparser
"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
"Moreover, p53 also could not interact with HAUSP and nucleolin in Mdm2-depleted cells ( xref )."
26238070
USP7 binds MDM2 and NCL. 2 / 2
| 2
sparser
"We also observed a HAUSP-nucleolin interaction in Mdm2-depleted cells under IR treatment."
26238070
sparser
"In contrary, knockdown of p53 did not affect HAUSP-nucleolin and HAUSP-Mdm2 interaction ( xref )."
26238070
TP53 binds USP7, MDM2, and MDM4. 1 / 1
| 1
sparser
"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
USP7 binds BAG6 and MDM2. 1 / 1
| 1
sparser
"We next wished to deduce whether Mdm2, Bat3 and HAUSP could also form a three-protein complex."
31647545
Ubiquitin binds TP53, USP7, and MDM2. 1 / 1
| 1
sparser
"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
USP7 binds MDM2 and 293T. 1 / 1
| 1
reach
"To this end, we conducted cell fractionation assays to determine the subcellular localization where HAUSP interacts with MDM2 in 293T cells."
28196907
USP2 binds USP7 and MDM2. 1 / 1
| 1
sparser
"USP10 is also associated with regulation of p53 localization and stability, however, unlike USP2 and USP7, it does not interact with MDM2 [ xref ]."
25972356
Ubiquitin binds TP53, USP7, MDM2, and TraF. 1 / 1
| 1
sparser
"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 – xref ]."
26460617
USP7 binds LIF, MDM2, and MDM4. 1 / 1
| 1
sparser
"Using the same cohort, we expanded the analysis to other TP53 signaling network genes [ xref ], and in contrast with previous findings, our results demonstrated no association of MDM2 , MDM4 , USP7 , and LIF polymorphisms with endometriosis-related infertility or IVF failure patients."
24427778
USP7 binds MDM2 and ATM. 1 / 1
| 1
sparser
"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 xref ."
28233861
TP53 binds USP7, CDKN1A, and MDM2. 1 / 1
| 1
sparser
"In addition to the altered levels of HDM2, p53 and p21 associated with its use, P22077 treatment also caused reduced levels of DNA damage proteins DDB1, RBX1, DCAF7 and DCAF11, all of which are subunits of E3 ligases, indicating a previously unknown functional link between USP7 and enzymes involved in DNA repair [ xref ]."
23822887
USP7 binds mutated MDM2. 1 / 1
| 1
reach
"Because the KQKQ MDM2 mutant bound HAUSP more strongly than did the wild-type MDM2 (XREF_FIG), we hypothesized that acetylation within the NLS may promote HAUSP recruitment on the acidic domain."
28196907
GST binds TP53, USP7, MDM2, and NCL. 1 / 1
| 1
sparser
"As expected, purified GST-p53 protein could bind Mdm2, nucleolin, and HAUSP ( xref , upper panel)."
26238070
USP10 binds USP7 and MDM2. 1 / 1
| 1
sparser
"Unlike HAUSP, USP10 did not interact with Mdm2 ( xref )."
20096447
USP7 binds DAXX, MDM2, and RASSF1. 1 / 1
| 1
sparser
"Song MS, et al. reported that RASSF1A could directly interact with Mdm2, HAUSP, and Daxx protein [ xref ]."
30615685
MDM2 activates USP7.
| 7
MDM2 activates USP7. 7 / 7
| 7
reach
"In vitro and in cancer cell lines, p300 mediated acetylation of MDM2 on Lys 182 and Lys 185 enabled HAUSP to bind, presumably deubiquitinate, and stabilize MDM2."
28196907
reach
"HAUSP plays pivotal roles in the stability of p53 and MDM2, raising HAUSP as a potential therapeutic target for tuning p53 mediated anti-tumor activity."
26077642
reach
"Both USP2 and USP7 and HAUSP target MDM2 and lead to its degradation XREF_BIBR."
27665737
reach
"P22077 downregulated USP7 targets MDM2, claspin, and Chk1 [XREF_BIBR] and inhibited neuroblastoma growth [XREF_BIBR], and P50429 inhibited HCT116 proliferation [XREF_BIBR, XREF_BIBR]."
30897496
reach
"Since MDM2 is the preferred target of USP7 under unstressed conditions [XREF_BIBR, XREF_BIBR], then logically, suppression of USP7 should destabilize MDM2."
23151129
reach
"These findings suggest that p300 mediated MDM2 acetylation within the NLS domain enables HAUSP to be recruited to the acidic domain, leading to deubiquitination of MDM2 (XREF_FIG)."
28196907
reach
"It has been shown that Mdm2 is the primary target of USP7 mediated stabilization."
23555268
MDM2 inhibits USP7.
| 4
MDM2 inhibits USP7. 4 / 4
| 4
reach
"As expected, MDM2, which is a known USP7 substrate, was decreased by RNAi-mediated knockdown of USP7 and this effect was also reversed by MG132."
33933455
reach
"As shown in XREF_FIG, both p53 and Mdm2 had decreased half-lives in hausp heterozygote MEF cells (lanes 5-8) compared with that in wild-type MEF cells (lanes 1-4)."
19946331
reach
"The results indicated that the mRNA level of MDM2, p21, PUMA, TP53INP1, TP53INP2, GDF15, and IGFBP3, is elevated upon knockdown of either ECT2 or USP7, albeit to variable extents, while the expression of TP53 is unchanged."
32929379
reach
"Interestingly, the Mdm2 level decreased after depletion of HAUSP (XREF_FIG, lane 6 versus lane 5), consistent with the previous finding that Mdm2 is a substrate of HAUSP, and Mdm2 is destabilized in hausp knockout cells."
21350561
MDM2 ubiquitinates USP7.
| 1
MDM2 ubiquitinates USP7. 1 / 3
| 1
reach
"This Lys869 ubiquitination site is close to the ICP0 interaction region, which supports the proposition that USP7 is ubiquitinated by ICP0 but not by MDM2."
32512887
EBNA1 affects MCMBP, MDM2, MDM4, TP53, UBE2E1, USP7, vIRF-1, and vIRF-4
| 1
TP53 binds UBE2E1, USP7, MCMBP, MDM2, MDM4, vIRF-1, EBNA1, and vIRF-4. 1 / 1
| 1
sparser
"USP7 can interact with p53, HDM2, HDMX, MCM-BP, UbE2E1, vIRF1, vIRF4, and EBNA1 through the TRAF-like domain [ xref , xref , xref , xref , xref , xref , xref ]."
33498168
DAXX affects RASSF1
| 1
USP7 binds DAXX, MDM2, and RASSF1. 1 / 1
| 1
sparser
"Song MS, et al. reported that RASSF1A could directly interact with Mdm2, HAUSP, and Daxx protein [ xref ]."
30615685
CDKN1A affects USP7
| 1
TP53 binds USP7, CDKN1A, and MDM2. 1 / 1
| 1
sparser
"In addition to the altered levels of HDM2, p53 and p21 associated with its use, P22077 treatment also caused reduced levels of DNA damage proteins DDB1, RBX1, DCAF7 and DCAF11, all of which are subunits of E3 ligases, indicating a previously unknown functional link between USP7 and enzymes involved in DNA repair [ xref ]."
23822887
BAG6 affects USP7
| 1
USP7 binds BAG6 and MDM2. 1 / 1
| 1
sparser
"We next wished to deduce whether Mdm2, Bat3 and HAUSP could also form a three-protein complex."
31647545
ATRX affects MDM2, RASSF5, TP53, TP63, TP73, and USP7
| 1
TP53 binds TP73, USP7, TP63, RASSF5, MDM2, and ATRX. 1 / 1
| 1
sparser
"The DAXX helical bundle (DHB) domain has been reported to interact with ATRX, RASSF1C, MDM2, HAUSP, P53, P63, and P73 (Escobar-Cabrera et al., xref ; Gostissa et al., xref ; Tang et al., xref ; Tang et al., xref )."
28875424
ATM affects USP7
| 1
USP7 binds MDM2 and ATM. 1 / 1
| 1
sparser
"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 xref ."
28233861
293T affects USP7
| 1
USP7 binds MDM2 and 293T. 1 / 1
| 1
reach
"To this end, we conducted cell fractionation assays to determine the subcellular localization where HAUSP interacts with MDM2 in 293T cells."
28196907