DNA Damage-induced MDMX Degradation Is Mediated by MDM2

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

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)45946-45953
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number46
DOIs
Publication statusPublished - Nov 14 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Kawai, H., Wiederschain, D., Kitao, H., Stuart, J., Tsai, K. K. C., & Yuan, Z. M. (2003). DNA Damage-induced MDMX Degradation Is Mediated by MDM2. Journal of Biological Chemistry, 278(46), 45946-45953. https://doi.org/10.1074/jbc.M308295200