Emi1 is required for cytostatic factor arrest in vertebrate eggs

• Published in: Nature (London) 2002-04, Vol.416 (6883), p.850-854
• Main Authors: Jackson, Peter K, Reimann, Julie D. R
• Format: Article
• Language: English
• Subjects: anaphase-promoting complex; Animals; APC protein; Biological and medical sciences; Calcium; Calcium - metabolism; Calcium - pharmacology; Cdc20 protein; Cdc20 Proteins; Cell Cycle - drug effects; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Extracts; Cyclin B - metabolism; cytostatic factor; Early stages. Segmentation. Gastrulation. Neurulation; Eggs; Embryology: invertebrates and vertebrates. Teratology; Embryos; Emi1 gene; Fundamental and applied biological sciences. Psychology; Inactivation; Meiosis - drug effects; Mitogen-Activated Protein Kinases - metabolism; Models, Biological; Oocytes - cytology; Oocytes - drug effects; Oocytes - metabolism; Precipitin Tests; Proteins; Proto-Oncogene Proteins c-mos - genetics; Proto-Oncogene Proteins c-mos - metabolism; Rats; Saccharomyces cerevisiae Proteins; Signal Transduction; Vertebrates; Xenopus laevis - metabolism; Xenopus Proteins
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/416850a

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 embryos. Fertilization causes a transient increase in cytoplasmic calcium concentration leading to CSF inactivation, APC activation, cyclin B destruction and mitotic exit. The APC activator Cdc20 is required for APC activation after fertilization. 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.