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 AAUAAA1,2,3,4. Although the signalling events that trigger c-mos mRNA polyadenylation and translation are unclear, they probably involve the activation of CPEB, the CPE binding factor5,6. 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.
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Acknowledgements
We thank E. J. Luna for her help with the two-dimensional separation of phospho-peptides, J. Leszyk for amino-acid sequencing, and the W. M. Keck Foundation for support of the Protein Chemistry Facility. We also thank M. Fernandez and members of the Richter laboratory for discussions and critically reading the manuscript. R.M. was supported by a Leukemia Society of America Special Fellow Award and L.E.L. was supported by a National Science Foundation Predoctoral Fellowship. This work was supported by grants from the NIH (to J.V.R. and J.D.R.).
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Mendez, R., Hake, L., Andresson, T. et al. Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA. Nature 404, 302–307 (2000). https://doi.org/10.1038/35005126
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DOI: https://doi.org/10.1038/35005126
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