Greatwall dephosphorylation and inactivation upon mitotic exit is triggered by PP1.

Date publication

avril 2016

Journal

Journal of cell science

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah

Tous les auteurs :
Ma S, Vigneron S, Robert P, Strub JM, Cianferani S, Castro A, Lorca T

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/26906418

Résumé

Entry into mitosis is induced by the activation of cyclin-B-Cdk1 and Greatwall (Gwl; also known as MASTL in mammals) kinases. Cyclin-B-Cdk1 phosphorylates mitotic substrates, whereas Gwl activation promotes the phosphorylation of the small proteins Arpp19 and ENSA. Phosphorylated Arpp19 and/or ENSA bind to and inhibit PP2A comprising the B55 subunit (PP2A-B55; B55 is also known as PPP2R2A), the phosphatase responsible for cyclin-B-Cdk1 substrate dephosphorylation, allowing the stable phosphorylation of mitotic proteins. Upon mitotic exit, cyclin-B-Cdk1 and Gwl kinases are inactivated, and mitotic substrates are dephosphorylated. Here, we have identified protein phosphatase-1 (PP1) as the phosphatase involved in the dephosphorylation of the activating site (Ser875) of Gwl. Depletion of PP1 from meioticXenopusegg extracts maintains phosphorylation of Ser875, as well as the full activity of this kinase, resulting in a block of meiotic and mitotic exit. By contrast, preventing the reactivation of PP2A-B55 through the addition of a hyperactive Gwl mutant (GwlK72M) mainly affected Gwl dephosphorylation on Thr194, resulting in partial inactivation of Gwl and in the incomplete exit from mitosis or meiosis. We also show that when PP2A-B55 is fully reactivated by depleting Arpp19, this protein phosphatase is able to dephosphorylate both activating sites, even in the absence of PP1.

Mots clés

Animals, CDC2 Protein Kinase, metabolism, Cyclin B, metabolism, Enzyme Activation, Female, Male, Meiosis, physiology, Mitosis, physiology, Ovum, metabolism, Phosphoproteins, metabolism, Phosphorylation, Protein Phosphatase 1, metabolism, Protein Phosphatase 2, metabolism, Protein-Serine-Threonine Kinases, genetics, Xenopus, Xenopus Proteins, genetics

Référence

J. Cell. Sci.. 2016 Apr;129(7):1329-39