Polo-like kinase-1 phosphorylates MDM2 at Ser260 and stimulates MDM2-mediated p53 turnover

Sylvia S. Dias, Carol Hogan, Anna Maria Ochocka, David W. Meek

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)

    Abstract

    The E3 ubiqutin ligase, murne double-minute clone 2 (MDM2), promotes the degradation of p53 under normal homeostatic conditions. Several serine residues within the acidic domain of MDM2 are phosphorylated to maintain its activity but become hypo-phosphorylated following DNA damage, leading to inactivation of MDM2 and induction of p53. However, the signalling pathways that mediate these phosphorylation events are not fully understood. Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (PLK1), phosphorylates MDM2 at one of these residues, Ser260, and stimulates MDM2-mediated turnover of p53. These data are consistent with the idea that deregulation of PLK1 during tumourigenesis may help suppress p53 function.

    Structured summary:

    MINT-7266353: MDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with PLK1 (uniprotkb:P53350) by pull down (MI:0096)

    MINT-7266344, MINT-7266329: MDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with PLK1 (uniprotkb:P53350) by anti bait coimmunoprecipitation (MI:0006)

    MINT-7266250: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) p53 (uniprotkb:P04637) by protein kinase assay (MI:0424)

    MINT-7266241, MINT-7266318: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) MDM2 (uniprotkb:P23804) by protein kinase assay (MI:0424)

    MINT-7266231, MINT-7266805, MINT-7266264, MINT-7266299: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) MDM2 (uniprotkb:Q00987) by protein kinase assay (MI:0424) (C) 2009 Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.

    Original languageEnglish
    Pages (from-to)3543-3548
    Number of pages6
    JournalFEBS Letters
    Volume583
    Issue number22
    DOIs
    Publication statusPublished - 19 Nov 2009

    Keywords

    • p53
    • Murne double-minute clone 2
    • Polo-like kinase-1
    • Phosphorylation
    • CULTURED-CELLS
    • PROTEIN
    • HDM2
    • BINDING
    • DOMAIN
    • PLK1
    • SITE
    • STABILITY
    • PATHWAY

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