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USP7 deubiquitinates MDM2. 106 / 108
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"In a variety of cancer research, USP7 can promote the deubiquitination of MDM2 and MDMX, inhibit p53 signaling, and inhibit cell cycle arrest and apoptosis, making USP7 a key target gene for cancer re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35523402
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"The protein DAXX is an important component of this multiprotein complex that regulates HAUSP mediated deubiquitination of Mdm2, and recent work now shows that the assembly of this complex is in part regulated by the protein RASSF1A."
19450511
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"USP7 preferentially causes the deubiquitination of MDM2 (an oncogenic E3 ligase), which subsequently causes ubiquitination of p53 (a tumor suppressor protein) and decreases its cellular level."
39435002
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"USP7 can normally de-ubiquitinate MDM2 resulting in reduced p53 levels, but tLT binding to USP7 negatively affects MDM2 levels, thereby increasing p53 [69]."
36672392
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"Further studies reveal that HAUSP can also deubiquitinate Mdm2."
31282934
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"Importantly, upon DNA damage, HAUSP is less efficient in the deubiquitination of Hdmx and Hdm2 ( Figure 6 A, compare lanes 5 and 6)."
15916963
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"We next questioned the mechanism by which the deubiquitination of Hdmx/Hdm2 by HAUSP could be impaired."
15916963
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"Herpesvirus associated ubiquitin specific protease (HAUSP, also known as USP7), a deubiquitylating enzyme of the ubiquitin specific processing protease family, specifically deubiquitylates both p53 and MDM2, hence playing an important yet enigmatic role in the p53-MDM2 pathway."
16402859
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"HAUSP can deubiquitylate MDM2, both in vivo and in vitro, and is required for the stability of MDM2 in normal cells [XREF_BIBR - XREF_BIBR]."
16402859
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"USP7 deubiquitinates several tumour suppressors (p53, PTEN, FOXO and claspin) and E3 ligases (MDM2, Mule and viral proteins ICP0) and therefore regulates important signalling pathways that are involved in tumorigenesis XREF_BIBR XREF_BIBR."
25960197
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"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
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"USP7 deubiquitinates MDM2, an E3 ligase of p53, and in turn destabilizes p53 (Colland et al., 2009)."
30486612
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"It is based on the fact that USP7 mainly deubiquitinates and stabilizes Mdm2 in unstressed cells."
26460617
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"Surprisingly, both the Gu group and the Vogelstein group reported that complete ablation of USP7 resulted in stabilization of p53; this is because USP7 deubiquitinates and stabilizes Mdm2 more potently under physiologic conditions [XREF_BIBR, XREF_BIBR] (XREF_FIG)."
27844253
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"USP7 can deubiquitylate Hdm2 and consequently degrade p53."
29786660
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"A number of DUBs can modulate p53 signals : USP7 deubiquitylates both p53 and MDM2, one of the ubiquitin ligases that ubiquitylates p53, thereby stabilizing both proteins."
27516771
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"The best-characterized of these enzymes is USP7, a nuclear DUB that deubiquitylates both p53 and MDM2 [102] ."
24704338
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"Subsequently, HAUSP was shown to deubiquitinate Mdm2 and Mdmx, thereby stabilizing these proteins."
16082221
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"53 Genetic and biochemical validation in cancer cells 54 , 55 have indicated that USP7 deubiquitinates and stabilizes the E3 ligase, MDM2."
38602256
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"It has been reported that the expression level of USP7 is elevated in several types of tumor cells.31 32 Overexpression of USP7 causes deubiquitination of HDM2 and degradation of P53, which can promote tumor progression."
40104064
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"Inhibition of USP7 promotes MDM2 ubiquitination and proteasomal degradation, ultimately leading to elevated levels of p53 and cell death."
35852517
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"Thus, HAUSP is unable to inhibit the autoubiquitination and destabilization of Hdm2 upon DNA damage."
15916963
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"USP7 deubiquitinates Mdm2 and p53, and its overexpression causes Mdm2 and p53 stabilization."
26460617
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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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"By ubiquitylation of p53, MDM2 promotes degradation of p53, and USP7 downregulates p53 by deubiquitylating and protecting MDM2 from degradation [23,24]."
37829803
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"For instance, Mdm2 could be deubiquitinated and stabilized by USP7 and further induce the ubiquitination and degradation of p53 [37, 38]."
39343961
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"Additionally, Mdm2, MdmX and p53 can be deubiquitinated by the HAUSP (herpesvirus associated ubiquitin specific protease) protein."
28690977
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"Additionally, MDM2 interacts with a specific ubiquitin protease, USP7, which can reverse MDM2 ubiquitination and prevent its degradation by the proteasome."
38275873
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"It has been reported that Hausp de-ubiquitinates Mdm2 and p53 [XREF_BIBR; XREF_BIBR]."
20153724
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"USP7 also can deubiquitinate Mdm2, a p53 chaperone molecule and inhibitor, thus inhibiting its degradation (Cummins et al., 2004; Xia et al., 2021)."
37251574
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"Ubiquitin specific protease 7 (USP7) deubiquitinates p53 and Hdm2 and regulates their stability."
26786098
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"[1597] USP7-mediated deubiquitination of Mdm2 as well as p53 by USP7 makes p53 hyperstable with an extended half-life."
40061651
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"In this complex, USP7 promotes continued Mdm2 deubiquitylation and stabilization thus supporting Mdm2 dependent p53 degradation."
22361354
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"This is accomplished by several deubiquitination enzymes including USP7 that deubiquitinates Mdm2 to stabilize p53 [XREF_BIBR] as well as USP10 and USP42 that can directly deubiquitinate p53 upon DNA damage [XREF_BIBR, XREF_BIBR]."
28208785
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"In unstressed cells, USP7 deubiquitinates the ubiquitin ligase HDM2 (or its mouse counterpart MDM2) to limit proteasomal degradation of HDM2 and its binding partner HDMX (MDMX in mice) (reviewed by [205])."
35608338
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"The unexpected result of p53 overexpression in USP7 knockout cells could be due because USP7 is also able to deubiquitinate MDM2 determining the steady-level of p53 [6,9,37,40] ."
28729047
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"A lack of USP7 dependent deubiquitylation of MDM2 may lead, through enhanced breakdown of MDM2, to accumulation of p53 in melanoma."
33869052
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"The same DUB can target proteins from the same pathway that exert opposing effects, for example Usp7 can deubiquitinate both p53 and its E3 ligase MDM2 depending on the circumstances."
25962961
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"Selfubiquitination is inhibited during times of nonstress by the deubiquitase HAUSP, an enzyme that specifically interacts with and deubiquitinates both Mdm2 and p53 in a mutually exclusive manner [XREF_BIBR - XREF_BIBR]."
20404858
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"Together, our data suggest that USP7 inhibition by P5091 induces HDM2 polyubiquitylation, and accelerate degradation of HDM2."
22975377
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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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"Several studies have demonstrated that HAUSP also deubiquitinates and elongates the half-life of Mdm2 as well as p53, and that these three proteins can form a complex XREF_BIBR XREF_BIBR."
26238070
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"For example, the de-ubiquitinating enzyme HAUSP (herpes virus-associated ubiquitin-specific protease) in conjunction with DAXX (death-domain-associated protein) has been demonstrated to inhibit Mdm2 a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19217357
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"Moreover, deubiquitination of either p53 or Mdm2 by HAUSP is apparently a critical event in these dynamic processes ( Li et al., 2004; Cummins et al., 2004 ), and additional cellular factors are neces[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15989956
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"USP7 preferentially deubiquitylates and stabilizes E3 ligase MDM2 (human ortholog HDM2), which negatively regulates the celebrated tumor suppressor p53 [6,7] ."
28216017
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"However, HAUSP also deubiquitinates MDM2 and reduction of HAUSP levels, either by RNA interference or by gene deletion, produces a complex phenotype [XREF_BIBR - XREF_BIBR]."
24143256
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"Under normal conditions, USP7 constantly deubiquitinates MDM2, which binds to p53, resulting in two outcomes: (i) MDM2 inhibits the transcription of p53 target genes; and (ii) MDM2 acts as an E3 ligas[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
33157193
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"USP7 plays a dual role in p53 regulation and may deubiquitylate either p53 or its negative regulator, MDM2 (Cummins et al. 2004; Li et al. 2002, 2004)."
27881599
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"On the other hand, Mdm2 levels are regulated by the USP7 protein that prevents Mdm2 self ubiquitylation and proteasomal degradation."
22361354
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"Because USP7 mainly deubiquitinates and stabilizes Mdm2 in unstressed cells, we believe that WDR79 may stimulate the USP7-Mdm2 axis more effectively than the USP7-p53 counterpart, thereby facilitating the proliferation of NSCLC cells despite the functional antagonism between Mdm2 and p53."
28406480
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"Importantly, HAUSP can deubiquitinate MDM2, MDMX, and p53."
25808808
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"However, USP7 also directly deubiquitylates the auto-polyubiquitylated MDM2, stabilising the E3 ligase as well as its substrate [XREF_BIBR]."
28900014
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"USP7 is a critical component of this pathway as it deubiquitinates and stabilizes both p53 and MDM2."
24239534
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"HAUSP not only deubiquitinates p53, but also Mdm2."
19450511
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"USP7 deubiquitinates both mdm2 (which enhances p53 degradation) and p53 (which inhibits p53 degradation)."
25191222
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"But HAUSP can also deubiquitylate and stabilize MDM2."
20076526
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"However, Mdm2 can also self-ubiquitylate which promotes its own degradation therefore releasing p53 from its regulatory control, although this is inhibited by USP7, which persistently deubiquitylates Mdm2."
21138959
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"USP7 can also deubiquitinate and stabilize Mdm2 providing an alternative level of p53 regulation ( Cummins et al., 2004; Li et al., 2004 )."
25444757
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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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"According to previous findings, when it enters the nucleus, the GMPS-USP7 complex is formed with ubiquitin-specific protease 7 (USP7), which can promote the degradation of the p53 protein by deubiquitinating the negative p53 regulatory protein MDM2 [41,42]."
37484410
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"20 , 21 It appears that, under non-stressed physiological conditions, USP7 prefers to bind to and deubiquitinate Mdm2, promoting degradation of p53."
36952348
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"The first structure corresponds to USP7 (also known as HAUSP, Herpes associated USP), a DUB that preferentially deubiquitinates MDM2 (Murine Double Minute 2), the ubiquitin ligase for the tumor suppressor p53, as well as p53 itself XREF_BIBR."
19243136
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"Inhibition of USP7 deubiquitinase function therefore promotes increased MDM2 ubiquitination, leading to MDM2 degradation and resulting in reduced p53 protein degradation and subsequent accumulation and activation."
37762082
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"Indeed, HAUSP can also deubiquitinate Mdm2, which has auto-ubiquitination activity and is inherently unstable [XREF_BIBR]."
21624367
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"USP7 (ubiquitin specific protease 7), which deubiquitinates HDM2, can lead to increased levels of HDM2 and decreased levels of p53."
22649774
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"With the collaboration of the adapter protein Daxx (death domain associated protein), USP7 also deubiquitinates the mouse double minute 2 (MDM2) oncogene, one of several E3s that mediate p53 proteasomal degradation."
17291557
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"However, it remains uncertain whether up-regulation of MDM2 by USP7 facilitates FoxO4-ubiquitinated degradation and subsequently promotes PDGF-induced PASMCs proliferation.Previous studies have reported that USP7 deubiquitinates and stabilizes E3 ubiquitin ligase MDM2, thereby promoting cell growth in ovarian cancer cells."
34552711
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"These contradictory findings were explained by the fact that USP7 could also deubiquitylate MDM2 in some settings, thus indirectly leading to p53 degradation."
24507714
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"Studies have shown that USP7 deubiquitinates HDM2 and maintains the deubiquitination state, further mediating p53 ubiquitination and degradation and resulting in decreased intracellular p53 levels ."
40169699
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"Since HAUSP also deubiquitinates Mdm2, the stoichiometry of both proteins is important."
19929178
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"This creates a situation where USP7 can either deubiquitinate and stabilise MDM2, promoting p53 ubiquitination and its proteasomal degradation XREF_BIBR, XREF_BIBR, or target p53, preventing degradation and activating the apoptotic pathway 26."
30651545
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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
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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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"Because HAUSP can deubiquitinate both p53 and Mdm2, the dynamic consequences are not straightforward."
15865937
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"USP7, an MDM2 deubiquitinase, deubiquitinates MDM2 and prolongs its half-life to inhibit the p53 tumor suppressor function [XREF_BIBR]."
27764791
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"Apart from p53, USP7 also deubiquitinates and stabilizes Hdm2 and HdmX, which are negative regulators of p53, indicating a complex regulatory mechanism."
25605410
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"In cancers that are caused by a dysregulated Hdm2 protein but retain WT p53, the ability to inhibit USP7 deubiquitination of Hdm2 is considered to be of therapeutic importance because Hdm2 degradation would lead to p53 stabilization and activation."
25605410
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"In this case, Usp7 antagonizes the ubiquitination of the E3 Hdm2."
25325686
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"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
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"USP7, also known as Herpes associated USP (HAUSP), deubiquitinates p53 and Mdm2 and is inhibited by the Epstein-Barr nuclear antigen 1 (EBNA1) protein of Epstein-Barr virus (EBV)."
19489724
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"In unstressed cells, USP7 deubiquitylates both p53 and MDM2 and contributes to a finely balanced state in which p53 is continuously degraded 58."
29657328
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"Another example of tight control of DUB stability by phosphorylation is observed for USP7, which deubiquitinates and stabilizes the E3 Ub ligase MDM2."
35764170
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"USP7 deubiquitinates and stabilizes MDM2, which promotes p53 degradation."
38689642
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"For USP7, even though the N-terminal TRAF-like domain does bind to mdm2 and p53, it is not essential for USP7’s deubiquitinating activity towards mdm2 and p53."
20816748
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"Both MDM2 and p53 are USP7 substrates, but USP7 mainly deubiquitinates MDM2 [ 32 ], leading to MDM2 upregulation and its function as an E3 ligase that promotes the ubiquitination of p53, which is ulti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32092586
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"4,18 Indeed, Hdm2 was shown to be deubiquitinated by USP7."
20713061
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"However, under stressful conditions (such as DNA damage), increased levels of USP7 are unable to prevent ubiquitin-mediated degradation of Hdm2 and HdmX, indicating that USP7 is unable to deubiquitina[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20713061
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"They can directly ubiquitinate p53 for degradation, and can also bind to the intracellular DUB ubiquitin-specific protease (USP) 7, which inhibits the deubiquitination of murine double minutes 2 (MDM2) by USP7 and stabilize and increase the content of MDM2 in cells."
34803084
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"USP7 promotes mdm2 de-ubiquitination, which in turn modulates p53 protein degradation."
28657542
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"USP7/HAUSP can deubiquitinate and stabilize both Mdm2 and p53 depending on cellular stress."
| PMC
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"USP7 is capable of binding to and deubiquitylating auto-ubiquitylated Hdm2, which leads to stabilization of Hdm2 and consequent degradation of p53."
23684893
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"Ubiquitin-specific peptidase 7 (USP7) deubiquitinates MDM2, preventing its degradation via the ubiquitin–proteasome system, thus offering an alternative approach to stabilization and upregulation [142]."
39767719
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"However, USP7 overexpression leads to more profound deubiquitination of MDM2 compared to that of p53, which results in p53 degradation and progression of tumorigenic processes [53]."
36428632
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"Deubiquitination of Mdm2 mediated by HAUSP (deubiquitinase herpesvirus-associated ubiquitin-specific protease) is required to maintain the stability and promote the function of Mdm2 as an E3 ligase fo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31606391
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"Quite a few studies have shown that USP7 promotes tumor cell development, progression, and metastasis by deubiquitinating the p53 negative regulatory protein MDM2, which decreases intracellular levels of p53 (44-47)."
36388031
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"On the one hand, USP7 can deubiquitinate and stabilize Mdm2, thereafter leading to p53 destabilization."
37438558
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"Foo et al. found that ARC degradation is dependent on the p53-induced ubiquitin E3 ligase MDM2 (65), which USP7 can deubiquitinate (66)."
36388031
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"Interestingly, USP7 can deubiquitinate both p53 and its negative regulator HDM2, an E3 ubiquitin ligase responsible for polyubiquitination and subsequent degradation of p53."
30807924
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"Mdm2, rather than p53, appears to be the preferred substrate of USP7, resulting in Mdm2 stabilization as USP7 antagonizes autoubiquitination of Mdm2 and consequently induces the degradation of p53 [XREF_BIBR, XREF_BIBR]."
20974139
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"Interestingly, USP7 deubiquitinated MDM2 and its target p53, likewise, our data indicated that UBP12/13 interact with CRY2 and COP1 simultaneously."
35700731
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"However, USP7 also deubiquitinates and stabilizes Mdm2, which is in fact a better binding partner of USP7 than p53."
28807825
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"MDM2 self-ubiquitinates, tagging itself for proteolysis, while USP7 deubiquitinates MDM2 to protect it from proteasomal degradation (Figure 4B)."
35796308
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"However, HAUSP also indirectly affects p53 stability and activity by associating with and deubiquitinating Hdm2, leading to Hdm2 stabilization."
15916963
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"Thus, in absence of stress, USP7 mainly deubiquitinates and stabilizes Mdm2, while to a minor extent USP7 also deubiquitinates and stabilizes p53 [XREF_BIBR]."
26460617
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"The same blot was reprobed with anti-Hdm2, which showed that HAUSP, but not HAUSP (C223S), also deubiquitinates Hdm2 in vivo ( Figure 4 B)."
15916963
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"This latter observation confirmed an earlier report showing in vitro deubiquitination of Hdm2 by HAUSP ( Li et al., 2004 )."
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