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

135 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

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DNA Damage
Chemical activation
Degradation
DNA
Proto-Oncogene Proteins c-mdm2
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry

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

DNA Damage-induced MDMX Degradation Is Mediated by MDM2. / Kawai, Hidehiko; Wiederschain, Dmitri; Kitao, Hiroyuki; Stuart, Jeremy; Tsai, Kelvin K C; Yuan, Zhi Min.

In: Journal of Biological Chemistry, Vol. 278, No. 46, 14.11.2003, p. 45946-45953.

Research output: Contribution to journalArticle

Kawai, H, Wiederschain, D, Kitao, H, Stuart, J, Tsai, KKC & Yuan, ZM 2003, 'DNA Damage-induced MDMX Degradation Is Mediated by MDM2', Journal of Biological Chemistry, vol. 278, no. 46, pp. 45946-45953. https://doi.org/10.1074/jbc.M308295200
Kawai H, Wiederschain D, Kitao H, Stuart J, Tsai KKC, Yuan ZM. DNA Damage-induced MDMX Degradation Is Mediated by MDM2. Journal of Biological Chemistry. 2003 Nov 14;278(46):45946-45953. https://doi.org/10.1074/jbc.M308295200
Kawai, Hidehiko ; Wiederschain, Dmitri ; Kitao, Hiroyuki ; Stuart, Jeremy ; Tsai, Kelvin K C ; Yuan, Zhi Min. / DNA Damage-induced MDMX Degradation Is Mediated by MDM2. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 46. pp. 45946-45953.
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