Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle
| Autor: | Thierry Lorca, Anna Castro, Estelle Brioudes, Andrew Burgess, Suzanne Vigneron, Jean-Claude Labbé, Cyril Bernis |
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| Přispěvatelé: | Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1) |
| Rok vydání: | 2010 |
| Předmět: |
Embryo
Nonmammalian Cdc25 Maturation-Promoting Factor Cyclin A Cyclin B Maturation promoting factor Cell Cycle Proteins Polo-like kinase Protein Serine-Threonine Kinases Xenopus Proteins Xenopus laevis 03 medical and health sciences CDC2 Protein Kinase Animals cdc25 Phosphatases [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Protein Phosphatase 2 Mitosis Metaphase 030304 developmental biology 0303 health sciences biology 030302 biochemistry & molecular biology Cell Biology Protein-Tyrosine Kinases Cell cycle Cell biology Mitotic exit biology.protein Signal Transduction |
| Zdroj: | Journal of Cell Science Journal of Cell Science, Company of Biologists, 2010, 123 (Pt 13), pp.2281-91. ⟨10.1242/jcs.064527⟩ |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.064527 |
| Popis: | International audience; Recent results indicate that regulating the balance between cyclin-B-Cdc2 kinase, also known as M-phase-promoting factor (MPF), and protein phosphatase 2A (PP2A) is crucial to enable correct mitotic entry and exit. In this work, we studied the regulatory mechanisms controlling the cyclin-B-Cdc2 and PP2A balance by analysing the activity of the Greatwall kinase and PP2A, and the different components of the MPF amplification loop (Myt1, Wee1, Cdc25) during the first embryonic cell cycle. Previous data indicated that the Myt1-Wee1-Cdc25 equilibrium is tightly regulated at the G2-M and M-G1 phase transitions; however, no data exist regarding the regulation of this balance during M phase and interphase. Here, we demonstrate that constant regulation of the cyclin-B-Cdc2 amplification loop is required for correct mitotic division and to promote correct timing of mitotic entry. Our results show that removal of Cdc25 from metaphase-II-arrested oocytes promotes mitotic exit, whereas depletion of either Myt1 or Wee1 in interphase egg extracts induces premature mitotic entry. We also provide evidence that, besides the cyclin-B-Cdc2 amplification loop, the Greatwall-PP2A pathway must also be tightly regulated to promote correct first embryonic cell division. When PP2A is prematurely inhibited in the absence of cyclin-B-Cdc2 activation, endogenous cyclin-A-Cdc2 activity induces irreversible aberrant mitosis in which there is, first, partial transient phosphorylation of mitotic substrates and, second, subsequent rapid and complete degradation of cyclin A and cyclin B, thus promoting premature and rapid exit from mitosis. |
| Databáze: | OpenAIRE |
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