14-3-3 Binding to Pim-phosphorylated Ser166 and Ser186 of human Mdm2-Potential interplay with the PKB/Akt pathway and p14(ARF)

Nicola T. Wood, David W. Meek, Carol MacKintosh

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    Here we show that 14-3-3 proteins bind to Pim kinase-phosphorylated Ser166 and Ser186 on the human E3 ubiquitin ligase mouse double minute 2 (Mdm2), but not protein kinase B (PKB)/Akt-phosphorylated Ser166 and Ser188. Pim-mediated phosphorylation of Ser186 blocks phosphorylation of Ser188 by PKB, indicating potential interplay between the Pim and PKB signaling pathways in regulating Mdm2. In cells, expression of Pim kinases promoted phosphorylation of Ser166 and Ser186, interaction of Mdm2 with endogenous 14-3-3s and p14(ARF), and also increased the amount of Mdm2 protein by a mechanism that does not require Pim kinase activities. The implications of these findings for regulation of the p53 pathway, oncogenesis and drug discovery are discussed. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)615-620
    Number of pages6
    JournalFEBS Letters
    Volume583
    Issue number4
    DOIs
    Publication statusPublished - 18 Feb 2009

    Keywords

    • 14-3-3
    • Cancer
    • Mdm2
    • Phosphorylation
    • Pim kinase
    • HDM2-MEDIATED DEGRADATION
    • STRUCTURAL BASIS
    • MULTIPLE SITES
    • P53 PATHWAY
    • IN-VIVO
    • MDM2
    • PROTEIN
    • KINASE
    • HDM2
    • AKT

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