MAPK inactivation is required for the G2 to M-phase transition of the first mitotic cell cycle

• Published in: The EMBO journal 1997-11, Vol.16 (21), p.6407-6413
• Main Authors: Abrieu, Ariane, Fisher, Daniel, Simon, Marie-Noélle, Dorée, Marcel, Picard, André
• Format: Article
• Language: English
• Subjects: Animals; CDC2 Protein Kinase - metabolism; Cyclin B - metabolism; cyclin B-cdc2 kinase; Dual Specificity Phosphatase 6; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - enzymology; Enzyme Activation; Female; Fertilization; Fungal Proteins - genetics; Fungal Proteins - metabolism; G2 Phase - physiology; G2 to M-phase transition; Male; MAP kinase inactivation; MAP Kinase Kinase Kinases; Meiosis - physiology; Metaphase - physiology; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - physiology; mitosis; Mitosis - physiology; Parthenogenesis - physiology; Protein Kinases - metabolism; Protein Tyrosine Phosphatases - pharmacology; Protein-Serine-Threonine Kinases - pharmacology; Recombinant Fusion Proteins - metabolism; Schizosaccharomyces pombe Proteins; Starfish - embryology; Transcription Factors - genetics; Transcription Factors - metabolism; Xenopus laevis - embryology; Zygote - cytology; Zygote - enzymology
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/16.21.6407

Down‐regulation of MAP kinase (MAPK) is a universal consequence of fertilization in the animal kingdom, although its role is not known. Here we show that MAPK inactivation is essential for embryos, both vertebrate and invertebrate, to enter first mitosis. Suppressing down‐regulation of MAPK at fertilization, for example by constitutively activating the upstream MAPK cascade, specifically suppresses cyclin B‐cdc2 kinase activation and its consequence, entry into first mitosis. It thus appears that MAPK functions in meiotic maturation by preventing unfertilized eggs from proceeding into parthenogenetic development. The most general effect of artificially maintaining MAPK activity after fertilization is prevention of the G2 to M‐phase transition in the first mitotic cell cycle, even though inappropriate reactivation of MAPK after fertilization may lead to metaphase arrest in vertebrates. Advancing the time of MAPK inactivation in fertilized eggs does not, however, speed up their entry into first mitosis. Thus, sustained activity of MAPK during part of the first mitotic cell cycle is not responsible for late entry of fertilized eggs into first mitosis.