Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3

Cynthia LeBron, Lihong Chen, Daniele Gilkes, Jiandong Chen

Research output: Contribution to journalArticle

Abstract

The MDM2 homolog MDMX is an important regulator of p53 during mouse embryonic development. DNA damage promotes MDMX phosphorylation, nuclear translocation, and degradation by MDM2. Here we show that MDMX copurifies with 14-3-3, and DNA damage stimulates MDMX binding to 14-3-3. Chk2-mediated phosphorylation of MDMX on S367 is important for stimulating 14-3-3 binding, MDMX nuclear import by a cryptic nuclear import signal, and degradation by MDM2. Mutation of MDMX S367 inhibits ubiquitination and degradation by MDM2, and prevents MDMX nuclear import. Expression of 14-3-3 stimulates the degradation of phosphorylated MDMX. Chk2 and 14-3-3 cooperatively stimulate MDMX ubiquitination and overcome the inhibition of p53 by MDMX. These results suggest that MDMX-14-3-3 interaction plays a role in p53 response to DNA damage by regulating MDMX localization and stability.

Original languageEnglish (US)
Pages (from-to)1196-1206
Number of pages11
JournalThe EMBO journal
Volume25
Issue number6
DOIs
StatePublished - Mar 22 2006
Externally publishedYes

Fingerprint

Cell Nucleus Active Transport
DNA Damage
Ubiquitination
Degradation
Phosphorylation
DNA
Embryonic Development
Mutation

Keywords

  • 14-3-3
  • Chk2
  • MDM2
  • MDMX
  • p53

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. / LeBron, Cynthia; Chen, Lihong; Gilkes, Daniele; Chen, Jiandong.

In: The EMBO journal, Vol. 25, No. 6, 22.03.2006, p. 1196-1206.

Research output: Contribution to journalArticle

LeBron, Cynthia ; Chen, Lihong ; Gilkes, Daniele ; Chen, Jiandong. / Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. In: The EMBO journal. 2006 ; Vol. 25, No. 6. pp. 1196-1206.
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