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USP7 deubiquitinates MDM2. 61 / 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
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"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
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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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"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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"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 (Refs 43, 44, 45)."
22088887
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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
reach
"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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"Additionally, Mdm2, MdmX and p53 can be deubiquitinated by the HAUSP (herpesvirus associated ubiquitin specific protease) protein."
28690977
signor
"Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins."
16082221
reach
"USP7 is a critical component of this pathway as it deubiquitinates and stabilizes both p53 and MDM2."
24239534
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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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"In this case, Usp7 antagonizes the ubiquitination of the E3 Hdm2."
25325686
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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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"USP7 promotes mdm2 de-ubiquitination, which in turn modulates p53 protein degradation."
28657542
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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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"Importantly, HAUSP can deubiquitinate MDM2, MDMX, and p53."
25808808
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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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"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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"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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"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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"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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"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 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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"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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"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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"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
reach
"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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"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 deubiquitinates both mdm2 (which enhances p53 degradation) and p53 (which inhibits p53 degradation)."
25191222
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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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"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) (Tang et al., 2006), USP7 also deubiquitinates the mouse double minute 2 (MDM2) oncogene, one of several E3s that mediate p53 proteasomal degradation."
17291557
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"Importantly, impaired deubiquitination of Hdmx and Hdm2 by HAUSP contributes to the DNA damage induced degradation of Hdmx and transient instability of Hdm2."
15916963
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"USP7/HAUSP can deubiquitinate and stabilize both Mdm2 and p53 depending on cellular stress."
| PMC
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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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"USP7 can deubiquitylate Hdm2 and consequently degrade p53."
29786660
reach
"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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"Because HAUSP can deubiquitinate both p53 and Mdm2, the dynamic consequences are not straightforward."
15865937
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"It has been reported that Hausp de-ubiquitinates Mdm2 and p53 [XREF_BIBR; XREF_BIBR]."
20153724
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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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"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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"But HAUSP can also deubiquitylate and stabilize MDM2."
20076526
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"It is based on the fact that USP7 mainly deubiquitinates and stabilizes Mdm2 in unstressed cells."
26460617
trips
"Subsequently, HAUSP was shown to deubiquitinate Mdm2 and Mdmx, thereby stabilizing these proteins."
16082221
reach
"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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"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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"Indeed, HAUSP can also deubiquitinate Mdm2, which has auto-ubiquitination activity and is inherently unstable [XREF_BIBR]."
21624367
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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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"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, 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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"Ubiquitin specific protease 7 (USP7) deubiquitinates p53 and Hdm2 and regulates their stability."
26786098
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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
reach
"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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"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