Program in Molecular Medicine; Department of Molecular Genetics and Microbiology
Amino Acid Sequence; Animals; Cell Differentiation; Eukaryotic Initiation Factor-4E; Humans; Mitotic Spindle Apparatus; Molecular Sequence Data; Oocytes; Phosphoamino Acids; Phosphorylation; Phosphoserine; Polyadenylation; Protein Binding; Protein Biosynthesis; RNA, Messenger; Sequence Alignment; Staphylococcal Protein A; Transcription Factors; Xenopus Proteins; Xenopus laevis
Life Sciences | Medicine and Health Sciences
Several cytoplasmic polyadenylation element (CPE)-containing mRNAs that are repressed in Xenopus oocytes become active during meiotic maturation. A group of factors that are anchored to the CPE are responsible for this repression and activation. Two of the most important are CPEB, which binds directly to the CPE, and Maskin, which associates with CPEB. In oocytes, Maskin also binds eukaryotic translation initiation factor 4E (eIF4E), an interaction that excludes eIF4G and prevents formation of the eIF4F initiation complex. When the oocytes are stimulated to reenter the meiotic divisions (maturation), CPEB promotes cytoplasmic polyadenylation. The newly elongated poly(A) tail becomes bound by poly(A) binding protein (PABP), which in turn binds eIF4G and helps it displace Maskin from eIF4E, thereby inducing translation. Here we show that Maskin undergoes several phosphorylation events during oocyte maturation, some of which are important for its dissociation from eIF4E and translational activation of CPE-containing mRNA. These sites are T58, S152, S311, S343, S453, and S638 and are phosphorylated by cdk1. Mutation of these sites to alanine alleviates the cdk1-induced dissociation of Maskin from eIF4E. Prior to maturation, Maskin is phosphorylated on S626 by protein kinase A. While this modification has no detectable effect on translation during oocyte maturation, it is critical for this protein to localize on the mitotic apparatus in somatic cells. These results show that Maskin activity and localization is controlled by differential phosphorylation.
DOI of Published Version
Mol Cell Biol. 2005 Sep;25(17):7605-15. Link to article on publisher's site
Molecular and cellular biology
Barnard, Daron C.; Cao, Quiping; and Richter, Joel D., "Differential phosphorylation controls Maskin association with eukaryotic translation initiation factor 4E and localization on the mitotic apparatus" (2005). Open Access Articles. 1412.