Phosphorylation of serine 392 in p53 is a common and integral event during p53 induction by diverse stimuli

Miranda L. Cox, David W. Meek

    Research output: Contribution to journalArticlepeer-review

    83 Citations (Scopus)

    Abstract

    Post-translational modifications play important roles during the stabilisation and activation of p53 by various genotoxic and non-genotoxic stresses. Ser392 has been reported to be a major UV-stimulated phosphorylation site that is modified through the p38 MAPK pathway in a manner that may involve recruitment of CK2. Here we show that phosphorylation of Ser392 is an integral event that occurs not only in response to UV. but also during the induction of p53 by a range of stimuli including treatment of cells with the MDM2 inhibitor, Nutlin 3a. Strikingly, phosphorylation of Ser392 and Ser33 was also observed following induction of the p53 pathway by ARF which has previously been thought to induce p53 in a phosphorylation-independent manner. The induction of Ser392 phosphorylation by diverse stimuli can be explained by a common mechanism in which its phosphorylation at a low rate, coupled with the rapid turnover of p53, limits the accumulation of phosphorylated molecules until a stimulus stabilises p53 and allows the Ser392-phosphorylated p53 to accumulate. We also provide biological evidence that Ser392 phosphorylation is not mediated by a UV-associated route involving p38 MAPK, either directly or indirectly via CK2. These data suggest that, physiologically, Ser392 may be phosphorylated by an, as yet, unidentified protein kinase. (C) 2009 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)564-571
    Number of pages8
    JournalCellular Signalling
    Volume22
    Issue number3
    DOIs
    Publication statusPublished - Mar 2010

    Keywords

    • p53
    • CK2
    • p38
    • Phosphorylation
    • Serine 392
    • CASEIN KINASE-II
    • TUMOR-SUPPRESSOR PROTEIN
    • SMALL-MOLECULE ANTAGONISTS
    • DNA-DAMAGE
    • IONIZING-RADIATION
    • IN-VITRO
    • POSTTRANSLATIONAL MODIFICATIONS
    • SER389 PHOSPHORYLATION
    • GAMMA-RADIATION
    • UV-RADIATION

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