IndraLab

Statements

MDM2 activates USP7. 10 / 10
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"Since MDM2 is the preferred target of USP7 under unstressed conditions [XREF_BIBR, XREF_BIBR], then logically, suppression of USP7 should destabilize MDM2."
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"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."
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"It has been shown that Mdm2 is the primary target of USP7 mediated stabilization."
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"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)."
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"Exposure of parental MCF7 cells to XL177A resulted in 737 DE genes, which strongly correlated with DE genes elicited by MDM2 inhibition with nutlin3a as well as knockout of USP7 in parental MCF7 cells (Figure 4d)."
35737447
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"Taken together, these data suggest that the residual Mdm2 not destabilized by HAUSP inhibition could be targeted to more potently and efficiently activate p53 protein levels and prevent tumor growth.Novel HAUSP inhibitors better modulate HAUSP functionDue to poor solubility and low potency of commercially available HAUSP inhibitors, we recently described the synthesis of a series of thiazole derivates [23] based on p5091 [20] and p22077 [18] inhibitors."
29616860
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"Both USP2 and USP7 and HAUSP target MDM2 and lead to its degradation XREF_BIBR."
27665737
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"This suggests that phosphorylation of Hdm2 and HdmX could modulate their interaction with USP7, since both Hdm2 and HdmX are phosphorylated by multiple kinases including ATM and ATR, following DNA dam[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20713061
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"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."
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"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]."
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