IndraLab

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USP7 inhibits MDM2. 29 / 31
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"Interestingly, severe ablation of USP7 expression diminished Mdm2 but increased Poleta (XREF_FIG)."
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"USP7 disrupts the equilibrium of the p53-dependent MDM2 axis, leading to the proteasomal degradation of p53 and ultimately decreasing the expression of PD-L1 on the surface of tumor cells.120, 121, 122 Several USP7 inhibitors are currently in preclinical trials and further studies are required."
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"USP7 directly regulates p53 stability or downregulates p53 by stabilizing MDM2."
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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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"A therapeutic strategy to discover senolytics that stabilize p53 are direct inhibition of MDM2 and the degradation of MDM2 promoted by USP7 inhibition.The major regulation of p53 is made by MDM2 and M[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In particular, inhibitors of the ubiquitin-specific protease 7 (USP7) have been shown to enhance the degradation of MDM2 and MDMX, liberating and activating p53 to exert its tumor-suppressive functions (15)."
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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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"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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"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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"3,4 These studies demonstrate that inactivation of USP7 induces Mdm2 degradation thus allowing for activation of p53 in tumor cells expressing wild-type p53."
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"Overexpression of HAUSP also reduces the inhibitory effect of Mdm2 on p53-dependent apoptosis."
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"The sequestration effect of polyQ-IRF on USP7 can attenuate the biological function of HDM2, directly reduce the ubiquitination and degradation of P53, and thereby prompt the P53 level."
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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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"On the other hand, polyQ-IRF also sequesters HDM2 together with USP7 (Figure 3), which down-regulates the function of HDM2 and thus enhances the P53 stability (Figure 9)."
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"Indeed, we also found that coexpression of HAUSP can prevent the Hdm2-mediated degradation of p53, whereas at the same time, Hdm2 levels are increased by ectopic HAUSP expression ( Figure 1 A )."
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"Loss of HAUSP mediated deubiquitination contributes to DNA damage induced destabilization of Hdmx and Hdm2."
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"It could be hypothesized that not the decrease in HAUSP activity triggers the degradation of Hdmx but rather an increase in Hdm2 activity."
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"XREF_BIBR HAUSP antagonizes the action of MDM2 on P53."
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"Another mechanism by which RASSF1A controls cell cycle and apoptosis is by the disruption of the MDM2–DAXX–HAUSP complex leading to MDM2 self-ubiquitination and stabilization of p53 [36] ."
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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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"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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"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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"USP7 also negatively regulates the stability of MDM2."
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"USP7 can also promote the degradation of MDM2 to inhibit the p53-mediated anti-tumor immune response."
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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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"Previous studies showed that USP7 inhibition promotes the degradation of MDM2 and reactivates p53 signaling [ 31 ]."
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"A study has shown that USP7 deubiquitinates and stabilizes E3 ubiquitin ligase MDM2, and thereby promotes MDM2-mediated ubiquitinated degradation of p53 and cell growth in ovarian cancer cells."
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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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