IndraLab

Statements

MDM2 bound to TP53 activates TP53. 27 / 27
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"In addition, HDM2 binding to p53 blocks its transactivation domain preventing p53 transcriptional activation of its target genes."
25965177
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"The binding of hdm2 to p53 induces the suppression and degradation of p53, as well as export p53 from the nucleus, thus hdm2 function as a negative regulator of p53."
24986024
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"Up-regulation of p53 protein in response to ribosomal stress is largely due to the disruption of interaction between p53 and MDM2, an oncogenic E3 ligase that not only targets p53 for proteasome mediated degradation but also inhibits the transactivation activity of p53."
24762395
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"Inhibition of p53 and Mdm2 interactions by small molecule (nutlin-3) or silencing Mdm2 did not rescue the p53 degradation, indicating that HCV infection induces degradation of p53 independent of the Mdm2 pathway."
29404458
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"XREF_BIBR, XREF_BIBR, XREF_BIBR In normal unstressed cells, p53 is bound to MDM2, which targets p53 for proteasomal degradation."
26226899
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"MDM2 may bind P53 and promote P53 degradation at baseline but stimulate P53 translation under stress XREF_BIBR."
22844496
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"Nutlin-3 inhibits the physical interaction between p53 and its inhibitor MDM2, and activates p53 responses in p53 wild-type cancer cells."
22170099
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"The first is the mdm-2 protein, a binding partner of p53 that targets p53 for rapid, proteasome mediated degradation and is considered as the universal regulator of p53 protein stability [31, 32]."
10605931
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"Nutlin-3a, a small molecule inhibitor of the p53 and MDM2 interaction, which promotes p53 reactivation, kills PEL cells in culture and has potent anti-tumor activity in mice bearing PEL tumors [XREF_BIBR, XREF_BIBR]."
25243371
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"HDM2 binds p53 at the transactivation domain of p53 and blocks its ability to activate transcription, serves as a ubiquitin ligase that promotes p53 degradation, and mediates the nuclear export of p53."
20736344
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"Although the Mdm2 protein binds to p53 to mediate p53 proteolysis, the effects of Mdm2 on TGF-beta sensitivity appear to be independent of p53 function, because expression of an Mdm2 mutant that failed to bind p53 also conferred resistance [XREF_BIBR]."
11250701
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"The abrogation of Hdm2 and p53 interaction using a small molecule Hdm2 inhibitor nutlin-3 or the downregulation of HIF2alpha via HIF2alpha specific shRNA or wild-type VHL reconstitution restores p53 function and reverses the resistance of CCRCC cells to Fas mediated and chemotherapy induced cell death."
19920202
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"These results are in keeping with reports that Ser20 phosphorylation can inhibit binding between MDM2 and p53 that then allows recruitment of the transcription coactivator p300 to p53."
28031409
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"The p53 protein is maintained in normal cells as an unstable protein, and the interaction of MDM2 and p53 has been shown to target p53 for degradation via a ubiquitin proteolytic pathway [5,6]."
10754200
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"The oncoprotein MDM2 binds p53 and negatively regulates its activity by inhibiting p53 transcriptional activity and translocation from the nucleus to the cytoplasm, and by enhancing p53 degradation vi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30041135
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"The generation of p53 mutations by Nutlin-3 during the development of resistance observed in these studies may be a specific response to Nutlin-3 mediated DNA damage rather than a general response to non genotoxic reactivation of p53 by MDM2 and p53 binding antagonists."
27323823
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"Several mechanisms are responsible for p53 induction, including MDM2 inactivation, interrupted interaction between p53 and MDM2, and activation of ubiquitin proteases."
25732823
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"First, Mdm2 causes rapid degradation of p53 through ubiquitination and proteasomal degradation; second, Mdm2 binds the N-terminal transactivation domain of p53, preventing transcriptional activation of p53 target genes."
22586610
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"These co-treatment results revealed that p53 degradation is due to its direct association with MDM2 because compounds are known to block the interaction between MDM2 and p53 could abolish the degradation of p53 but not MDM2 by WB214[37]."
33862513
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"MDM2 directly binds to p53 and represses its transcriptional activity promoting p53 degradation."
27837610
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"Phosphorylation of p53 renders its main partner Mdm2 incapable of tightly binding p53, which is necessary to target p53 for degradation via the ubiquitin proteasome pathway."
23554695
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"MDM2 binds NS independently of p53, and mediates association of NS and p53."
19033382
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"Many anticancer drug development efforts in the past decade have therefore been devoted to the discovery and optimization of small molecules that selectively disrupt the interaction between MDM2 and p53, which could provide, in principle, a potent means to restore p53 function in tumor cells with wild-type p53."
24262662
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"A quite recent study showed that the RING finger domain of MDM2 binds to p53 mRNA in vivo, which increases p53 synthesis."
19411066
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"The protein MDM2 binds to p53, inhibits its transcriptional activation, causes nuclear export and acts as an E3 ligase to target p53 for proteasomal degradation."
20818437
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"Nutlin-3 is a compound that disrupts the binding between MDM2 and p53 leading to activation and accumulation of free p53 [XREF_BIBR]."
21209724
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"Although quite complex, key regulators of p53 include the human homolog of murine double minute-2 (HDM2), which directs p53 for degradation, and p14ARF, which disrupts the interaction between MDM2 and p53, thus freeing p53 to act XREF_BIBR."
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