title: Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1).
abstract: Mammalian oocytes are arrested in prophase of the first meiotic division. Progression into the first meiotic division is driven by an increase in the activity of maturation-promoting factor (MPF). In mouse oocytes, we find that early mitotic inhibitor 1 (Emi1), an inhibitor of the anaphase-promoting complex (APC) that is responsible for cyclin B destruction and inactivation of MPF, is present at prophase I and undergoes Skp1-Cul1-F-box/betaTrCP-mediated destruction immediately after germinal vesicle breakdown (GVBD). Exogenous Emi1 or the inhibition of Emi1 destruction in prophase-arrested oocytes leads to a stabilization of cyclin B1-GFP that is sufficient to trigger GVBD. In contrast, the depletion of Emi1 using morpholino oligonucleotides increases cyclin B1-GFP destruction, resulting in an attenuation of MPF activation and a delay of entry into the first meiotic division. Finally, we show that Emi1-dependent effects on meiosis I require the presence of Cdh1. These observations reveal a novel mechanism for the control of entry into the first meiotic division: an Emi1-dependent inhibition of APC(Cdh1).
authors.affiliation: Department of Physiology, University College London, London WC1E 6BT, England, UK. p.marangos@ucl.ac.uk
authors.forename: Petros
authors.initials: P
authors.lastname: Marangos
authors.forename: Emmy W
authors.initials: EW
authors.lastname: Verschuren
authors.forename: Ruby
authors.initials: R
authors.lastname: Chen
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jackson
authors.forename: John
authors.initials: J
authors.lastname: Carroll
mesh_terms: D016475:3T3 Cells; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D044783:F-Box Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008540:Meiosis; D049469:Meiotic Prophase I; D000090204:Mesothelin; D008677:Metaphase; D051379:Mice; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D019926:Cyclin B; C498959:Emi1 protein, mouse; D044783:F-Box Proteins; C498960:FBXO5 protein, human; C000715528:Msln protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044843:SKP Cullin F-Box Protein Ligases; D000090204:Mesothelin