Phosphorylation of MDMX Mediated by Akt Leads to Stabilization and Induces 14-3-3 Binding

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2008 Mar 22

PMID 18356162

Citations 40

Authors

Vanessa Lopez-Pajares

Mihee M Kim

Zhi-Min Yuan

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Understanding the interaction of 14-3-3 proteins with hDMX and hDM2: a structural and biophysical study.

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