title: Greatwall dephosphorylation and inactivation upon mitotic exit is triggered by PP1.
abstract: 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.
authors.affiliation: Université de Montpellier, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 1919 Route de Mende, Montpellier 34293, Cedex 5, France. Equipe Labellisée 'Ligue Contre le Cancer'
authors.forename: Sheng
authors.initials: S
authors.lastname: Ma
authors.affiliation: Université de Montpellier, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 1919 Route de Mende, Montpellier 34293, Cedex 5, France. Equipe Labellisée 'Ligue Contre le Cancer'
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vigneron
authors.affiliation: Université de Montpellier, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 1919 Route de Mende, Montpellier 34293, Cedex 5, France. Equipe Labellisée 'Ligue Contre le Cancer'
authors.forename: Perle
authors.initials: P
authors.lastname: Robert
authors.affiliation: Laboratoire de Spectrométrie de Masse Bio-Organique, Institut Pluridisciplinaire Hubert Curien, UMR 7178, 25 rue Becquerel, Strasbourg F67087, Cedex 2, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Strub
authors.affiliation: Laboratoire de Spectrométrie de Masse Bio-Organique, Institut Pluridisciplinaire Hubert Curien, UMR 7178, 25 rue Becquerel, Strasbourg F67087, Cedex 2, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Cianferani
authors.affiliation: Université de Montpellier, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 1919 Route de Mende, Montpellier 34293, Cedex 5, France. Equipe Labellisée 'Ligue Contre le Cancer' anna.castro@crbm.cnrs.fr thierry.lorca@crbm.cnrs.fr.
authors.forename: Anna
authors.initials: A
authors.lastname: Castro
authors.affiliation: Université de Montpellier, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 1919 Route de Mende, Montpellier 34293, Cedex 5, France. Equipe Labellisée 'Ligue Contre le Cancer' anna.castro@crbm.cnrs.fr thierry.lorca@crbm.cnrs.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lorca
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D008297:Male; D008540:Meiosis / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D010063:Ovum / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019926:Cyclin B; D010750:Phosphoproteins; D029867:Xenopus Proteins; C064321:cyclic AMP-regulated phosphoprotein 19; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; C584831:ppp2r2a protein, Xenopus laevis
keywords: Greatwall; Meiotic exit; Mitotic exit; PP1; PP2A-B55