title: A critical balance between Cyclin B synthesis and Myt1 activity controls meiosis entry in Xenopus oocytes.
abstract: In fully grown oocytes, meiosis is arrested at first prophase until species-specific initiation signals trigger maturation. Meiotic resumption universally involves early activation of M phase-promoting factor (Cdc2 kinase-Cyclin B complex, MPF) by dephosphorylation of the inhibitory Thr14/Tyr15 sites of Cdc2. However, underlying mechanisms vary. In Xenopus oocytes, deciphering the intervening chain of events has been hampered by a sensitive amplification loop involving Cdc2-Cyclin B, the inhibitory kinase Myt1 and the activating phosphatase Cdc25. In this study we provide evidence that the critical event in meiotic resumption is a change in the balance between inhibitory Myt1 activity and Cyclin B neosynthesis. First, we show that in fully grown oocytes Myt1 is essential for maintaining prophase I arrest. Second, we demonstrate that, upon upregulation of Cyclin B synthesis in response to progesterone, rapid inactivating phosphorylation of Myt1 occurs, mediated by Cdc2 and without any significant contribution of Mos/MAPK or Plx1. We propose a model in which the appearance of active MPF complexes following increased Cyclin B synthesis causes Myt1 inhibition, upstream of the MPF/Cdc25 amplification loop.
authors.affiliation: UPMC Université Paris 06, UMR7622-Biologie du Développement, 9 quai Saint Bernard, 75005 Paris, France.
authors.forename: Melina
authors.initials: M
authors.lastname: Gaffré
authors.forename: Alain
authors.initials: A
authors.lastname: Martoriati
authors.forename: Naima
authors.initials: N
authors.lastname: Belhachemi
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Chambon
authors.forename: Evelyn
authors.initials: E
authors.lastname: Houliston
authors.forename: Catherine
authors.initials: C
authors.lastname: Jessus
authors.forename: Anthi
authors.initials: A
authors.lastname: Karaiskou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019926:Cyclin B / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019926:Cyclin B; D029867:Xenopus Proteins; C095970:MYT1 kinase, Xenopus; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases