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Phosphorylation of MDMX mediated by Akt leads to stabilization and induces 14-3-3 binding.

The critical tumor suppressor p53 is mutated or functionally inactivated in nearly all cancers. We have shown previously that the MDM2-MDMX complex functions as an integral unit in targeting p53 for degradation. Here we identify the small protein 14-3-3 as a binding partner of MDMX, which binds at the C terminus (Ser367) in a phosphorylation-dependent manner. Importantly, we demonstrate that the serine/threonine kinase Akt mediates phosphorylation of MDMX at Ser367. This phosphorylation leads to stabilization of MDMX and consequent stabilization of MDM2. Previous studies have shown that Akt phosphorylates and stabilizes MDM2. Our data suggest that stabilization of MDMX by Akt may be an alternative mechanism by which Akt up-regulates MDM2 protein levels and exerts its oncogenic effects on p53 in tumor cells.

Pubmed ID: 18356162


  • Lopez-Pajares V
  • Kim MM
  • Yuan ZM


The Journal of biological chemistry

Publication Data

May 16, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: R01CA85679-02
  • Agency: NIEHS NIH HHS, Id: T32ES07155

Mesh Terms

  • 14-3-3 Proteins
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Sequence Homology, Amino Acid
  • Tumor Suppressor Protein p53