IndraLab

Statements

TP53 bound to MDM2 activates TP53. 22 / 22
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"Later, Zawacka-Pankau et al. showed that in cultured cells, PpIX binds to p53 at its N-terminus and disrupts the interaction between p53 and HDM2 (the human homologue of MDM2), thereby disrupting HDM2 's negative regulation of p53."
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"N3 increases p53 levels by inhibiting the interaction between p53 and Mdm2, an E3 ubiquitin ligase that targets p53 for proteasomal degradation (Vassilev et al., 2004)."
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"Nutlin-3 activates p53 by inhibiting the interaction between p53 and MDM2 (inducer of p53 proteasomal degradation) (Vassilev et al., 2004)."
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"Upon induction of DNA damage, the inhibitory interaction between p53 and Mdm2 is disrupted by phosphorylation of both proteins, resulting in p53 accumulation [XREF_BIBR]."
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"This interaction between MDM2 and p53 also allows MDM2 to shuttle p53 out of the nucleus in a RING-domain dependent manner."
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"In an inactive state, p53 is bound to Mdm2, which antagonizes the transcriptional activity of p53, induces its ubiquitylation, and promotes nuclear export of p53 [43,44]."
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"Furthermore, high levels of phosphorylation of p53 at Serine 15 (Ser15), modulate cell cycle checkpoint kinase Ataxia-Telangiectasia Mutated (ATM) and Ataxia-Telangiectasia and Rad3 related (ATR) that impede MDM2 binding to p53 and subsequently promote p53 accumulation and activation in response to DNA damage [XREF_BIBR, XREF_BIBR]."
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"Next we used a dual luciferase reporter assay to measure theactivation of the TP53 pathway in response to treatment with three DNA damage inducing agents (mitomycin C, doxorubicin, or UV-C) or nutlin-3a, which inhibits the interaction between MDM2 and TP53 and thus promotes TP53 signaling."
27642012
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"Separation of the p53-MDM2 complex can lead to ROS accumulation, while JNK can activate the downstream gene p53 [95]."
31639019
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"MDM4 negatively regulates p53 in both MDM2 dependent and -independent manners; MDM4 interacts with MDM2 and promotes MDM2 mediated ubiquitination and degradation of p53, and also interacts with p53 to suppress the transcriptional activities of p53."
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"MDM2 binds to a tumour suppressor protein p53 and induces ubiquitin dependent degradation of p53, which inhibits p53 functions XREF_BIBR."
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"Thus, CDR1as binding disrupts the p53 and MDM2 complex to prevent p53 from ubiquitination and degradation."
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"Nutlins are cis-imidazoline analogs that target the interaction between MDM2 and p53 preventing the degradation of p53 and allowing the p53 to accumulate."
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"MDM2 binds p53 at its transactivation domain to block its ability to activate transcription, promotes the nuclear export of p53, and may enhance p53 degradation by serving as a ubiquitin ligase."
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"P53 alpha-Helix mimetics antagonize p53 and MDM2 interaction and activate p53."
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"Mdm2 binds to P53 and leads to complete elimination of P53 through proteolytic degradation."
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"One of the major endogenous negative regulators of p53 in humans is hDM2, a ubiquitin E3 ligase that binds to p53 causing proteasomal p53 degradation."
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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."
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"Nutlins were originally identified as potent small molecules that inhibit the interaction between p53 and MDM2, which promote p53 degradation XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"To investigate the efficacy of PFT-α inhibition of p53 in cancer cells, we reactivated p53 by Nutlin-3, which inhibits the E3-ubiquitin ligase MDM2 by direct binding, disrupts the p53-MDM2 complex and prevents subsequent p53 degradation by the proteasome ."
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"E3 ligases PHF1 and RFWD3 prevent complex formation between MDM2 and p53 thus promoting the stability of p53."
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"Such phosphorylation might, for instance, weaken the interaction between p53 and Mdm2 (S. Shieh, C. Prives), thereby rescuing p53 from the inhibitory effects of Mdm2."
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