IndraLab

Statements

USP7 inhibits MDM2. 15 / 17
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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."
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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 ."
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"Partial reductions in HAUSP levels lead to destabilization of p53, whereas more complete reductions may cause MDM2 destabilization and p53 accumulation."
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"25 USP7 deficiency in mouse embryonic fibroblasts (MEFs) greatly reduces the half-life of MDM2 and activates p53."
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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."
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"USP7 also negatively regulates the stability of MDM2."
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"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."
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"Interestingly, severe ablation of USP7 expression diminished Mdm2 but increased Poleta (XREF_FIG)."
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"XREF_BIBR HAUSP antagonizes the action of MDM2 on P53."
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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."
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"This hypothesis is supported by our finding that proteasome inhibition with MG132 abrogated USP7 inhibition‐induced downregulation of MDM2 and upregulation of p53 in SnCs."
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"However, the phosphorylation is counterbalanced by ATM-dependent protein phosphatase PPMG1, and USP7 dephosphorylation causes MDM2 degradation and p53 stabilization (Figure 3d) [95]."
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"In fact, a genetic knockout of USP7 caused depletion of MDM2 and, despite the aforementioned rescue effect of USP7 on p53, effectively stabilized p53."
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"The role of USP7 in promoting degradation of HDM2 resulting in increased levels of p53 and p21 is documented in multiple models (Chauhan et al., 2012; Kon et al., 2010) ."
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"Loss of HAUSP mediated deubiquitination contributes to DNA damage induced destabilization of Hdmx and Hdm2."
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