Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA

Nature. 2000 Mar 16;404(6775):302-7. doi: 10.1038/35005126.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Aurora Kinases
  • Catalysis
  • Cell Cycle Proteins
  • Gene Expression Regulation*
  • Molecular Sequence Data
  • Mutagenesis
  • Oocytes / cytology
  • Oocytes / metabolism
  • Oogenesis
  • Phosphopeptides / metabolism
  • Phosphorylation
  • Progesterone / pharmacology
  • Protein Biosynthesis
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-mos / genetics*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Serine / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Xenopus
  • Xenopus Proteins*
  • mRNA Cleavage and Polyadenylation Factors*

Substances

  • Cell Cycle Proteins
  • Cpeb1 protein, Xenopus
  • Phosphopeptides
  • RNA, Messenger
  • RNA-Binding Proteins
  • Transcription Factors
  • Xenopus Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • Serine
  • Progesterone
  • Protein Kinases
  • AURKA protein, Xenopus
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-mos