Abstract
Until fertilization, the meiotic cell cycle of vertebrate eggs is arrested at metaphase of meiosis II by a cytoplasmic activity termed cytostatic factor (CSF)1, which causes inhibition of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets mitotic cyclins—regulatory proteins of meiosis and mitosis—for degradation2,3. Recent studies indicate that Erp1/Emi2, an inhibitor protein for the APC/C, has an essential role in establishing and maintaining CSF arrest4,5,6, but its relationship to Mos, a mitogen-activated protein kinase (MAPK) kinase kinase that also has an essential role in establishing CSF arrest7 through activation of p90 ribosomal S6 kinase (p90rsk)8,9, is unclear. Here we report that in Xenopus eggs Erp1 is a substrate of p90rsk, and that Mos-dependent phosphorylation of Erp1 by p90rsk at Thr 336, Ser 342 and Ser 344 is crucial for both stabilizing Erp1 and establishing CSF arrest in meiosis II oocytes. Semi-quantitative analysis with CSF-arrested egg extracts reveals that the Mos-dependent phosphorylation of Erp1 enhances, but does not generate, the activity of Erp1 that maintains metaphase arrest. Our results also suggest that Erp1 inhibits cyclin B degradation by binding the APC/C at its carboxy-terminal destruction box10, and this binding is also enhanced by the Mos-dependent phosphorylation. Thus, Mos and Erp1 collaboratively establish and maintain metaphase II arrest in Xenopus eggs. The link between Mos and Erp1 provides a molecular explanation for the integral mechanism of CSF arrest in unfertilized vertebrate eggs.
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26 April 2007
The addition of the word 'kinase' in the 9th line of the abstract
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Acknowledgements
We thank J. L. Maller and M. Iwabuchi for antibodies, M. Mori for CA- and KD-p90rsk2 proteins, K. Tachibana and E.Okumura for discussions, and M. J. Lohka and L. A. Jaffe for reading the manuscript. This work was also supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan to K.O. and T.K.
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Nishiyama, T., Ohsumi, K. & Kishimoto, T. Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs. Nature 446, 1096–1099 (2007). https://doi.org/10.1038/nature05696
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DOI: https://doi.org/10.1038/nature05696
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