Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA.
Full-grown Xenopus oocytes arrest at the G2/M border of meiosis I. Progesterone breaks this arrest, leading to the resumption of the meiotic cell cycles and maturation of the oocyte into a fertilizable egg. In these oocytes, progesterone interacts with an unidentified surface-associated receptor, which induces a non-transcriptional signalling pathway that stimulates the translation of dormant c-mos messenger RNA. Mos, a mitogen-activated protein (MAP) kinase kinase kinase, indirectly activates MAP kinase, which in turn leads to oocyte maturation. The translational recruitment of c-mos and several other mRNAs is regulated by cytoplasmic polyadenylation, a process that requires two 3' untranslated regions, the cytoplasmic polyadenylation element (CPE) and the polyadenylation hexanucleotide AAUAAA. Although the signalling events that trigger c-mos mRNA polyadenylation and translation are unclear, they probably involve the activation of CPEB, the CPE binding factor. Here we show that an early site-specific phosphorylation of CPEB is essential for the polyadenylation of c-mos mRNA and its subsequent translation, and for oocyte maturation. In addition, we show that this selective, early phosphorylation of CPEB is catalysed by Eg2, a member of the Aurora family of serine/threonine protein kinases.
Mendez
R
R
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655, USA.
Hake
L E
LE
Andresson
T
T
Littlepage
L E
LE
Ruderman
J V
JV
Richter
J D
JD
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D064127:Aurora Kinases; D002384:Catalysis; D018797:Cell Cycle Proteins; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009866:Oogenesis; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors
D018797:Cell Cycle Proteins; C490388:Cpeb1 protein, Xenopus; D010748:Phosphopeptides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D012694:Serine; D011374:Progesterone; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos