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Article Dans Une Revue Journal of Cell Science Année : 2018

A PIM-CHK1 signaling pathway regulates PLK1 phosphorylation and function during mitosis

Résumé

Although the kinase CHK1 is a key player in the DNA damage response (DDR), several studies have recently provided evidence of DDR-independent roles of CHK1, in particular following phosphorylation of its S280 residue. Here, we demonstrate that CHK1 S280 phosphorylation is cell cycle-dependent and peaks during mitosis. We found that this phosphorylation was catalyzed by the kinase PIM2, whose protein expression was also increased during mitosis. Importantly, we identified polo-like kinase 1 (PLK1) as a direct target of CHK1 during mitosis. Genetic or pharmacological inhibition of CHK1 reduced the activating phosphorylation of PLK1 on T210, and recombinant CHK1 was able to phosphorylate T210 of PLK1 in vitro Accordingly, S280-phosphorylated CHK1 and PLK1 exhibited similar specific mitotic localizations, and PLK1 was co-immunoprecipitated with S280-phosphorylated CHK1 from mitotic cell extracts. Moreover, CHK1-mediated phosphorylation of PLK1 was dependent on S280 phosphorylation by PIM2. Inhibition of PIM proteins reduced cell proliferation and mitotic entry, which was rescued by expressing a T210D phosphomimetic mutant of PLK1. Altogether, these data identify a new PIM-CHK1-PLK1 phosphorylation cascade that regulates different mitotic steps independently of the CHK1 DDR function.This article has an associated First Person interview with the first author of the paper.

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Dates et versions

hal-02329399 , version 1 (23-10-2019)

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Kévin Adam, Maëlle Cartel, Mireille Lambert, Laure David, Lingli Yuan, et al.. A PIM-CHK1 signaling pathway regulates PLK1 phosphorylation and function during mitosis. Journal of Cell Science, 2018, 131 (15), pp.jcs213116. ⟨10.1242/jcs.213116⟩. ⟨hal-02329399⟩
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