Mutant p53 Sequestration of the MDM2 Acidic Domain Inhibits E3 Ligase Activity.
作者： Leixiang Yang , Tanjing Song , Qian Cheng , Lihong Chen , Jiandong Chen
DOI: 10.1128/MCB.00375-18
关键词:
摘要: Missense p53 mutants often accumulate in tumors and drive progression through gain of function. MDM2 efficiently degrades wild-type but fails to degrade mutant tumor cells. Previous studies revealed that inhibits autoubiquitination, suggesting the interaction E3 activity. Recent work showed activity is stimulated by intramolecular between RING acidic domains. Here, we show p53-MDM2 complex, core domain binds with significantly higher avidity than p53. The complex deficient catalyzing ubiquitin release from activated E2 conjugating enzyme. An construct extra copies resistant inhibition promotes ubiquitination degradation. results suggest interferes autoactivation mechanism MDM2, contributing reduced increased accumulation
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