title: Regulation of Cyclin A protein in meiosis and early embryogenesis.
abstract: In contrast to the extensive analysis of the regulation of Cyclin B protein levels during developmental progression through meiosis in oogenesis, little is known about Cyclin A. Repression of cyclin A translation early in prophase I in Drosophila is important to maintain the oocyte in meiosis, and this has been shown to be mediated by deadenylation of the mRNA and inhibition by the Bruno repressor. We find that at oocyte maturation as meiosis resumes, Cyclin A protein reappears, coincident with polyadenylation of the mRNA and loss of Bruno repressor. Cyclin A is multiphosphorylated in a pattern consistent with autophosphorylation, and this form accumulates aberrantly in metaphase I if the Cortex form of the Anaphase Promoting Complex/Cyclosome is inactive. The PAN GU (PNG) kinase positively promotes translation of Cyclin A, beginning in oogenesis, an earlier onset than previously recognized. After egg activation and the completion of meiosis, PNG promotes further polyadenylation of cyclin A mRNA and appears to antagonize repression of translation by the PUMILIO inhibitor. Epistasis studies with png; apc mutants indicate that PNG acts solely to promote translation, rather than having a parallel function to inhibit degradation. These studies reveal multiple levels of posttranscriptional regulation of Cyclin A protein by translational and proteolytic control during oocyte maturation and the onset of embryogenesis.
authors.affiliation: Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Vardy
authors.forename: Jillian A
authors.initials: JA
authors.lastname: Pesin
authors.forename: Terry L
authors.initials: TL
authors.lastname: Orr-Weaver
mesh_terms: D000818:Animals; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D004625:Embryo, Nonmammalian; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D008540:Meiosis; D009865:Oocytes / Q000166:cytology; D010766:Phosphorylation; D026723:Polyadenylation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D019925:Cyclin A; D012333:RNA, Messenger