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: Contribution to journalArticle査読

140 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)45946-45953
ページ数8
ジャーナルJournal of Biological Chemistry
278
46
DOI
出版ステータス出版済み - 11 14 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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