DNA Damage-induced MDMX Degradation Is Mediated by MDM2

Hidehiko Kawai, Dmitri Wiederschain, Hiroyuki Kitao, Jeremy Stuart, Kelvin K C Tsai, Zhi Min Yuan

研究成果: 雜誌貢獻文章同行評審

140 引文 斯高帕斯(Scopus)

摘要

Although genetic studies have demonstrated that MDMX is essential to maintain p53 activity at low levels in non-stressed cells, it is unknown whether MDMX regulates p53 activation by DNA damage. We show here that DNA damage-induced p53 induction is associated with rapid down-regulation of the MDMX protein. Significantly, interference with MDMX down-regulation results in the suppression of p53 activation by genotoxic stress. We also demonstrate that DNA damage-induced MDMX reduction is mediated by MDM2, which targets MDMX for proteasomal degradation by a distinct mechanism that permits preferential MDMX degradation and therefore ensures optimal p53 activation.
原文英語
頁(從 - 到)45946-45953
頁數8
期刊Journal of Biological Chemistry
278
發行號46
DOIs
出版狀態已發佈 - 11月 14 2003
對外發佈

ASJC Scopus subject areas

  • 生物化學

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