Chk1 inhibition activates p53 through p38 MAPK in tetraploid cancer cells

Ilio Vitale, Laura Senovilla, Lorenzo Galluzzi, Alfredo Criollo, Sonia Vivet, Maria Castedo, Guido Kroemer

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    28 Citations (Scopus)

    Résumé

    We have previously shown that tetraploid cancer cells succumb through a p53-dependent apoptotic pathway when checkpoint kinase 1 (Chk1) is depleted by small interfering RNAs (siRNAs) or inhibited with 7-hydroxystaurosporine (UCN-01). Here, we demonstrate that Chk1 inhibition results in the activating phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Depletion of p38 MAPK by transfection with a siRNA targeting the α isoform of p38 MAPK (p38α MAPK) abolishes the phosphorylation of p53 on serines 15 and 46 that is induced by Chk1 knockdown. The siRNA-mediated downregulation and pharmacological inhibition of p38α MAPK (with SB 203580) also reduces cell death induced by Chk1 knockdown or UCN-01. These results underscore the role of p38 MAPK as a pro-apoptotic kinase in the p53-dependant pathway for the therapeutic elimination of polyploidy cells.

    langue originaleAnglais
    Pages (de - à)1956-1961
    Nombre de pages6
    journalCell Cycle
    Volume7
    Numéro de publication13
    Les DOIs
    étatPublié - 1 juil. 2008

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