CDC14B acts through FZR1 (CDH1) to prevent meiotic maturation of mouse oocytes.
Meiotic maturation in oocytes is a prolonged process that is unique because of cell cycle arrests at prophase of meiosis I (MI) and at metaphase of meiosis II (MII). Fluctuations in cyclin-dependent kinase 1 (CDK1/CDC2A) activity govern meiotic progression, yet little is known about how these fluctuations are achieved. CDC14 is a highly conserved dual-specificity phosphatase that counteracts the function of proteins phosphorylated by CDK. Mammals contain two CDC14 homologs, CDC14A and CDC14B. We report that CDC14B localizes with the meiotic spindle in mouse oocytes, and (unlike somatic cells) it does not localize in the nucleolus. Oocytes that overexpress CDC14B are significantly delayed in resuming meiosis and fail to progress to MII, whereas oocytes depleted of CDC14B spontaneously resume meiosis under conditions that normally inhibit meiotic resumption. Depletion of FZR1 (CDH1), a regulatory subunit of the anaphase-promoting complex/cyclosome that targets cyclin B1 (CCNB1) for ubiquitin-mediated proteolysis, partially restores normal timing of meiotic resumption in oocytes with excess CDC14B. These studies also reveal that experimentally altering CDC14B levels generates eggs with abnormal spindles and with chromosome alignment perturbations. Our data indicate that CDC14B is a negative regulator of meiotic resumption and may regulate MI in mouse oocytes.
Schindler
Karen
K
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Schultz
Richard M
RM
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism / Q000502:physiology; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D009865:Oocytes / Q000378:metabolism / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics
C534700:Ccnb1 protein, mouse; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; C577585:Fzr1 protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase; C541950:CDC14B protein, mouse; D054637:Dual-Specificity Phosphatases