Involvement of p38α in the mitotic progression of p53-/- tetraploid cells

Ilio Vitale, Mohamed Jemaà, Laura Senovilla, Lorenzo Galluzzi, Santiago Rello-Varona, Didier Metivier, Hugues Ripoche, Vladimir Lazar, Philippe Dessen, Maria Castedo, Guido Kroemer

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    11 Citations (Scopus)

    Abstract

    The tumor suppressor protein p53 plays a major role in preserving genomic stability. p53 suppresses a pathway leading from normal diploidy to neoplastic aneuploidy (via an intermediate metastable stage of tetraploidy) at two levels: first by preventing the generation/survival of tetraploid cells, and second by repressing their aberrant multipolar division. Here, we report the characterization of p53-/- tetraploid cells, which-at difference with both their p53-/- diploid and their p53+/+ tetraploid counterparts - manifest a marked hyperphosporylation of the mitogen-activated protein kinase MApK14 (best known as p38α) that is particularly strong during mitosis. In p53-/- tetraploid cells, phosphorylated p38α accumulated at centrosomes during the metaphase and at midbodies during the telophase. Selective knockdown or pharmacological inhibition of p38α had a dramatic effect on p53-/- (but not p53+/+) tetraploids, causing the activation of the spindle assembly checkpoint, an arrest during the metaphase, a major increase in abnormal bipolar and monopolar mitoses, as well as an increment in the generation of multinuclear cells. We conclude that the mitotic progression of p53-/- (but not p53+/+) tetraploids heavily relies on p38α, revealing a novel function for this protein in the context of aneuploidizing cell divisions.

    Original languageEnglish
    Pages (from-to)2895-2901
    Number of pages7
    JournalCell Cycle
    Volume9
    Issue number14
    DOIs
    Publication statusPublished - 15 Jul 2010

    Keywords

    • Aneuploidy
    • Apoptosis
    • Centrosome
    • Colon carcinoma
    • MOS

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