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Emi1 is required for cytostatic factor arrest in vertebrate eggs

Nature volume 416, pages 850–854 (2002)Cite this article

Abstract

Vertebrate eggs are arrested at metaphase of meiosis II with stable cyclin B and high cyclin B/Cdc2 kinase activity. The ability of the anaphase-promoting complex/cyclosome (APC), an E3 ubiquitin ligase, to trigger cyclin B destruction and metaphase exit is blocked in eggs by the activity of cytostatic factor (CSF) (reviewed in ref. 1). CSF was defined as an activity in mature oocytes that caused mitotic arrest when injected into dividing embryos2. Fertilization causes a transient increase in cytoplasmic calcium concentration leading to CSF inactivation, APC activation, cyclin B destruction and mitotic exit3. The APC activator Cdc20 is required for APC activation after fertilization4,5. We show here that the APCcdc20 inhibitor Emi1 (ref. 6) is necessary and sufficient to inhibit the APC and to prevent mitotic exit in CSF-arrested eggs. CSF extracts immunodepleted of Emi1 degrade cyclin B, and exit from mitosis prematurely in the absence of calcium. Addition of Emi1 to these Emi1-depleted extracts blocks premature inactivation of the CSF-arrested state. Emi1 is required to arrest unfertilized eggs at metaphase of meiosis II and seems to be the long-sought mediator of CSF activity.

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Figure 1: Emi1 is sufficient to prevent release from CSF block in the presence of Ca2+.
Figure 2: Emi1 is required for CSF arrest.
Figure 3: Addition of exogenous Cdc20 to CSF extracts activates cyclin B destruction and mitotic exit in the absence of calcium.
Figure 4: Model.

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References

  1. Masui, Y. The elusive cytostatic factor in the animal egg. Nature Rev. Mol. Cell Biol. 1, 228–232 (2000)

    Article  CAS  Google Scholar 

  2. Masui, Y. & Markert, C. L. Cytoplasmic control of nuclear behaviour during meiotic maturation of frog oocytes. J. Exp. Zool. 177, 129–145 (1971)

    Article  CAS  Google Scholar 

  3. Murray, A. W., Solomon, M. J. & Kirschner, M. W. The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. Nature 339, 280–286 (1989)

    Article  ADS  CAS  Google Scholar 

  4. Lorca, T. et al. Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts. EMBO J. 17, 3565–3575 (1998)

    Article  CAS  Google Scholar 

  5. Vorlaufer, E. & Peters, J. M. Regulation of the cyclin B degradation system by an inhibitor of mitotic proteolysis. Mol. Biol. Cell 9, 1817–1831 (1998)

    Article  CAS  Google Scholar 

  6. Reimann, J. D. et al. Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 105, 645–655 (2001)

    Article  CAS  Google Scholar 

  7. Sagata, N., Daar, I., Oskarsson, M., Showalter, S. D. & Vande Woude, G. F. The product of the mos proto-oncogene as a candidate ‘initiator’ for oocyte maturation. Science 245, 643–646 (1989)

    Article  ADS  CAS  Google Scholar 

  8. Yew, N., Mellini, M. L. & Vande Woude, G. F. Meiotic initiation by the mos protein in Xenopus. Nature 355, 649–652 (1992)

    Article  ADS  CAS  Google Scholar 

  9. Colledge, W. H., Carlton, M. B., Udy, G. B. & Evans, M. J. Disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs. Nature 370, 65–68 (1994)

    Article  ADS  CAS  Google Scholar 

  10. Hashimoto, N. et al. Parthenogenetic activation of oocytes in c-mos-deficient mice. Nature 370, 68–71 (1994)

    Article  ADS  CAS  Google Scholar 

  11. Furuno, N. et al. Suppression of DNA replication via Mos function during meiotic divisions in Xenopus oocytes. EMBO J. 13, 2399–2410 (1994)

    Article  CAS  Google Scholar 

  12. Gross, S. D. et al. The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90Rsk. Curr. Biol. 10, 430–438 (2000)

    Article  CAS  Google Scholar 

  13. Bhatt, R. R. & Ferrell, J. E. Jr protein kinase p90 Rsk as an essential mediator of cytostatic factor activity. Science 286, 1362–1365 (1999)

    Article  CAS  Google Scholar 

  14. Gross, S. D., Schwab, M. S., Lewellyn, A. L. & Maller, J. L. Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk. Science 286, 1365–1367 (1999)

    Article  CAS  Google Scholar 

  15. Haccard, O. et al. Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase. Science 262, 1262–1265 (1993)

    Article  ADS  CAS  Google Scholar 

  16. Shibuya, E. K. & Ruderman, J. V. Mos induces the in vitro activation of mitogen-activated protein kinases in lysates of frog oocytes and mammalian somatic cells. Mol. Biol. Cell 4, 781–790 (1993)

    Article  CAS  Google Scholar 

  17. King, R. W. et al. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81, 279–288 (1995)

    Article  CAS  Google Scholar 

  18. Sudakin, V. et al. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol. Biol. Cell 6, 185–197 (1995)

    Article  CAS  Google Scholar 

  19. Shah, J. V. & Cleveland, D. W. Waiting for anaphase: Mad2 and the spindle assembly checkpoint. Cell 103, 997–1000 (2000)

    Article  CAS  Google Scholar 

  20. Chen, R. H., Waters, J. C., Salmon, E. D. & Murray, A. W. Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274, 242–246 (1996)

    Article  ADS  CAS  Google Scholar 

  21. Sharp-Baker, H. & Chen, R. H. Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity. J. Cell Biol. 153, 1239–1250 (2001)

    Article  CAS  Google Scholar 

  22. Abrieu, A. et al. Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106, 83–93 (2001)

    Article  CAS  Google Scholar 

  23. Sagata, N., Watanabe, N., Vande Woude, G. F. & Ikawa, Y. The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs. Nature 342, 512–518 (1989)

    Article  ADS  CAS  Google Scholar 

  24. Castro, A. et al. Cyclin B/cdc2 induces c-Mos stability by direct phosphorylation in Xenopus oocytes. Mol. Biol. Cell 12, 2660–2671 (2001)

    Article  CAS  Google Scholar 

  25. Watanabe, N., Hunt, T., Ikawa, Y. & Sagata, N. Independent inactivation of MPF and cytostatic factor (Mos) upon fertilization of Xenopus eggs. Nature 352, 247–248 (1991)

    Article  ADS  CAS  Google Scholar 

  26. Lorca, T. et al. Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Nature 366, 270–273 (1993)

    Article  ADS  CAS  Google Scholar 

  27. Taieb, F. E., Gross, S. D., Lewellyn, A. L. & Maller, J. L. Activation of the anaphase-promoting complex and degradation of cyclin B is not required for progression from meiosis I to II in Xenopus oocytes. Curr. Biol. 11, 508–513 (2001)

    Article  CAS  Google Scholar 

  28. Guadagno, T. M. & Ferrell, J. E. Jr Requirement for MAPK activation for normal mitotic progression in Xenopus egg extracts. Science 282, 1312–1315 (1998)

    Article  ADS  CAS  Google Scholar 

  29. Ferrell, J. E. Jr Xenopus oocyte maturation: new lessons from a good egg. BioEssays 21, 833–842 (1999)

    Article  Google Scholar 

  30. Murray, A. W. Cell cycle extracts. Methods Cell Biol. 36, 581–605 (1991)

    Article  CAS  Google Scholar 

  31. Sohaskey, M. L. & Ferrell, J. E. Jr Distinct, constitutively active MAPK phosphatases function in Xenopus oocytes: implications for p42 MAPK regulation in vivo. Mol. Biol. Cell 10, 3729–3743 (1999)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank T. Hunt for Xcyclin B antibodies; E. Kramer and J. Peters for XCdc20 antibodies and construct; H. Schulman for CaMKIIα cDNA; H. Yu for D-box peptide; Ferrell laboratory members for technical assistance; and J. Peters and J. Ferrell for comments on the manuscript.

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  1. Departments of Pathology, Microbiology and Immunology, Stanford University School of Medicine, 300 Pasteur Drive, California, Stanford, 94305-5324, USA

    Julie D. R. Reimann & Peter K. Jackson

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Correspondence to Peter K. Jackson.

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Reimann, J., Jackson, P. Emi1 is required for cytostatic factor arrest in vertebrate eggs. Nature 416, 850–854 (2002). https://doi.org/10.1038/416850a

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