Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

New insight into metaphase arrest by cytostatic factor: from establishment to release

Abstract

Since the discovery of cytostatic factor (CSF) 35 years ago, significant progress has been made in identifying molecular components of CSF activity and the mechanism of CSF-induced metaphase II arrest (CSF arrest). This short review focuses on recent discoveries in the field and discusses the implication of these results for a general picture of CSF establishment and release. One recent focus is on the cyclin E/Cdk2 pathway. The discovery of a downstream target for cyclin E/Cdk2, the spindle checkpoint protein Mps1, provides insight into how cyclin E/Cdk2 contributes to CSF arrest. The anaphase promoting complex/cyclosome (APC/C) inhibitor Emi2 is another recent focus of work in the field. It is now clear that not only is degradation of Emi2 critical for CSF release, but its abrupt accumulation during meiosis II (M II) is also required for the establishment of CSF arrest. Thus, by discrete pathways of APC/C inhibition operative during CSF arrest, the stability of cell cycle arrest in the egg appears to be reinforced by multiple mechanisms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Abrieu A, Magnaghi-Jaulin L, Kahana JA, Peter M, Castro A, Vigneron S et al. (2001). Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106: 83–93.

    Article  CAS  Google Scholar 

  • Bhatt RR, Ferrell Jr JE . (1999). The protein kinase p90 rsk as an essential mediator of cytostatic factor activity. Science 286: 1362–1365.

    Article  CAS  Google Scholar 

  • D'Angiolella V, Costanzo V, Gottesman ME, Avvedimento EV, Gautier J, Grieco D . (2001). Role for cyclin-dependent kinase 2 in mitosis exit. Curr Biol 11: 1221–1226.

    Article  CAS  Google Scholar 

  • Fisk HA, Winey M . (2001). The mouse Mps1p-like kinase regulates centrosome duplication. Cell 106: 95–104.

    Article  CAS  Google Scholar 

  • Grimison B, Liu J, Lewellyn AL, Maller JL . (2006). Metaphase arrest by cyclin E/Cdk2 requires the spindle checkpoint kinase Mps 1. Curr Biol 16: 1968–1973.

    Article  CAS  Google Scholar 

  • Hansen DV, Tung JJ, Jackson PK . (2006). CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. Proc Natl Acad Sci USA 103: 608–613.

    Article  CAS  Google Scholar 

  • Liu J, Grimison B, Lewellyn AL, Maller JL . (2006). The APC/C inhibitor Emi2 is essential for meiotic but not mitotic cell cycles. J Biol Chem 281: 34736–34741.

    Article  CAS  Google Scholar 

  • Liu J, Maller JL . (2005). Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor. Curr Biol 15: 1458–1468.

    Article  CAS  Google Scholar 

  • Lorca T, Cruzalegui FH, Fesquet D, Cavadore JC, Mery J, Means A et al. (1993). Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Nature 366: 270–273.

    Article  CAS  Google Scholar 

  • Madgwick S, Hansen DV, Levasseur M, Jackson PK, Jones KT . (2006). Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis. J Cell Biol 174: 791–801.

    Article  CAS  Google Scholar 

  • Masui Y, Markert CL . (1971). Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J Exp Zool 177: 129–145.

    Article  CAS  Google Scholar 

  • Ohsumi K, Koyanagi A, Yamamoto TM, Gotoh T, Kishimoto T . (2004). Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest. Proc Natl Acad Sci USA 101: 12531–12536.

    Article  CAS  Google Scholar 

  • Phillips KP, Petrunewich MA, Collins JL, Booth RA, Liu XJ, Baltz JM . (2002). Inhibition of MEK or cdc2 kinase parthenogenetically activates mouse eggs and yields the same phenotypes as Mos(−/−) parthenogenotes. Dev Biol 247: 210–223.

    Article  CAS  Google Scholar 

  • Rauh NR, Schmidt A, Bormann J, Nigg EA, Mayer TU . (2005). Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation. Nature 437: 1048–1052.

    Article  CAS  Google Scholar 

  • Reimann JD, Jackson PK . (2002). Emi1 is required for cytostatic factor arrest in vertebrate eggs. Nature 416: 850–854.

    Article  CAS  Google Scholar 

  • Rempel RE, Sleight SB, Maller JL . (1995). Maternal Xenopus Cdk2–cyclin E complexes function during meiotic and early embryonic cell cycles that lack a G1 phase. J Biol Chem 270: 6843–6855.

    Article  CAS  Google Scholar 

  • Roy LM, Haccard O, Izumi T, Lattes BG, Lewellyn AL, Maller JL . (1996). Mos proto-oncogene function during oocyte maturation in Xenopus. Oncogene 12: 2203–2211.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Schmidt A, Duncan PI, Rauh NR, Sauer G, Fry AM, Nigg EA et al. (2005). Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity. Genes Dev 19: 502–513.

    Article  CAS  Google Scholar 

  • Schmidt A, Rauh NR, Nigg EA, Mayer TU . (2006). Cytostatic factor: an activity that puts the cell cycle on hold. J Cell Sci 119(Part 7): 1213–1218.

    Article  CAS  Google Scholar 

  • Sharp-Baker H, Chen RH . (2001). 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.

    Article  CAS  Google Scholar 

  • Shoji S, Yoshida N, Amanai M, Ohgishi M, Fukui T, Fujimoto S et al (2006). Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20. EMBO J 25: 834–845.

    Article  CAS  Google Scholar 

  • Tung JJ, Hansen DV, Ban KH, Loktev AV, Summers MK, Adler III JR et al (2005). A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs. Proc Natl Acad Sci USA 102: 4318–4323.

    Article  CAS  Google Scholar 

  • Tunquist BJ, Eyers PA, Chen LG, Lewellyn AL, Maller JL . (2003). Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest. J Cell Biol 163: 1231–1242.

    Article  CAS  Google Scholar 

  • Tunquist BJ, Maller JL . (2003). Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. Genes Dev 17: 683–710.

    Article  CAS  Google Scholar 

  • Tunquist BJ, Schwab MS, Chen LG, Maller JL . (2002). The spindle checkpoint kinase bub1 and cyclin e/cdk2 both contribute to the establishment of meiotic metaphase arrest by cytostatic factor. Curr Biol 12: 1027–1033.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J L Maller.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, J., Grimison, B. & Maller, J. New insight into metaphase arrest by cytostatic factor: from establishment to release. Oncogene 26, 1286–1289 (2007). https://doi.org/10.1038/sj.onc.1210203

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210203

Keywords

This article is cited by

Search

Quick links