title: Control of timing of embryonic M-phase entry and exit is differentially sensitive to CDK1 and PP2A balance.
abstract: Harmonious embryo development requires precise coordination between the timing of the cell cycle and the developmental program. Cyclin accumulation determines the timing of the cell cycle M-phase entry and its degradation determines the timing of the M-phase exit. It is well known that CDK1 and PP2A also govern M-phase entry. However, it is unknown how this kinase and phosphatase regulate the precise timing of events at the beginning of the M-phase and how they cooperate with cyclin metabolism. Here we use Xenopus laevis one-cell embryo cell-free extract experiments to answer this question critical for understanding the regulation of embryo development. Using, separately, low concentrations of the chemical inhibitor of CDK1, RO3306 (RO), or the inhibitor of phosphatases, okadaic acid (OA), we show that moderately diminished CDK1 or PP2A activities results in a delay and an acceleration respectively, of M-phase entry. Simultaneous diminution of CDK1 and PP2A activities results in an intermediate timing of M-phase entry, prolongs the duration of M-phase and diminishes the dynamics of cyclin B2 degradation. We thus show, for the first time, that equilibrium between CDK1 and PP2A specifies the timing of M-phase entry and exit and regulates the dynamics of cyclin B degradation upon M-phase exit in Xenopus laevis first embryonic mitosis.
authors.affiliation: CNRS, UMR 6290, Institute of Genetics and Development of Rennes, Cell Cycle Group, Rennes, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Dika
authors.forename: Damian
authors.initials: D
authors.lastname: Dudka
authors.forename: Claude
authors.initials: C
authors.lastname: Prigent
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Tassan
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kloc
authors.forename: Jacek Z
authors.initials: JZ
authors.lastname: Kubiak
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002474:Cell-Free System / Q000378:metabolism; D056765:Cyclin B2 / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology; D047108:Embryonic Development / Q000502:physiology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects*; D019319:Okadaic Acid / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D056765:Cyclin B2; D011804:Quinolines; C512984:RO 3306; D013844:Thiazoles; D029867:Xenopus Proteins; C523014:ccnb2 protein, Xenopus; D019319:Okadaic Acid; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2; C584831:ppp2r2a protein, Xenopus laevis