title: Successive recruitment of p-CDC25B-Ser351 and p-cyclin B1-Ser123 to centrosomes contributes to the release of mouse oocytes from prophase I arrest.
abstract: BACKGROUND
  The molecular mechanism that controls the activation of Cyclin B1-CDK1 complex has been widely investigated. It is generally believed that CDC25B acts as a "starter phosphatase" of mitosis. In this study, we investigate the sequential regulation of meiotic resumption by CDC25B and Cyclin B1 in mouse oocytes.
  
  
  RESULTS
  Injection of mRNAs coding for CDC25B-Ser351A and/or Cyclin B1-Ser123A shows a more potent maturation-inhibiting ability than their respective wild type. Co-injection of mRNAs coding for phosphor-mimic CDC25B-Ser351D and Cyclin B1-Ser123D can rescue this prophase I arrest induced by CDC25B-Ser351A or Cyclin B1-Ser123A. In addition, p-CDC25B-Ser351 is co-localized at the microtubule-organizing centers (MTOCs) with Aurora kinase A (AURKA) during maturation and p-Cyclin B1-Ser123 is only captured on MTOCs shortly before germinal vesicle breakdown (GVBD). Depletion of AURKA not only resulted in metaphase I (MI) spindle defects and anaphase I (AI) abnormal chromosomes separation but also prevented the phosphorylation of CDC25B-Ser351 at centrosomes. AURKA depletion induced deficiencies of spindle assembly and progression to MII can be rescued by CDC25B-Ser351D mRNA injection.
  
  
  CONCLUSIONS
  AURKA induced phosphorylation and recruitment of CDC25B to MTOCs prior to p-Cyclin B1-Ser123, and this sequential regulation is essential for the commitment of the oocytes to resume meiosis.
authors.affiliation: Department of Biochemical and Molecular Biology, China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Feng
authors.forename: Dahai
authors.initials: D
authors.lastname: Yu
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Didi
authors.initials: D
authors.lastname: Wu
authors.forename: Minglin
authors.initials: M
authors.lastname: Jin
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Wang
authors.forename: Bingzhi
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D049469:Meiotic Prophase I / Q000502:physiology*; D051379:Mice; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: C534700:Ccnb1 protein, mouse; D056744:Cyclin B1; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; C517006:Cdc25b protein, mouse; D020687:cdc25 Phosphatases
keywords: CDC25B; Cyclin B1; maturation-promoting factor; meiotic maturation; oocyte