title: Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity.
abstract: Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.
authors.forename: Ibtissem
authors.initials: I
authors.lastname: Nabti
authors.forename: Petros
authors.initials: P
authors.lastname: Marangos
authors.forename: Jenny
authors.initials: J
authors.lastname: Bormann
authors.forename: Nobuaki R
authors.initials: NR
authors.lastname: Kudo
authors.forename: John
authors.initials: J
authors.lastname: Carroll
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002478:Cells, Cultured; D002842:Chromatids / Q000378:metabolism; D020090:Chromosome Segregation; D005260:Female; D018386:Kinetochores / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins / Q000378:metabolism; D049469:Meiotic Prophase I; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009865:Oocytes / Q000201:enzymology; D049468:Prometaphase; D064249:Securin / Q000378:metabolism
chemical_list: D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C578005:PTTG1 protein, mouse; D064249:Securin; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase; D020928:Mitogen-Activated Protein Kinases