A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs.
Unfertilized vertebrate eggs are arrested in metaphase of meiosis II with high cyclin B/Cdc2 activity to prevent parthenogenesis. Until fertilization, exit from metaphase is blocked by an activity called cytostatic factor (CSF), which stabilizes cyclin B by inhibiting the anaphase-promoting complex (APC) ubiquitin ligase. The APC inhibitor early mitotic inhibitor 1 (Emi1) was recently found to be required for maintenance of CSF arrest. We show here that exogenous Emi1 is unstable in CSF-arrested Xenopus eggs and is destroyed by the SCF(betaTrCP) ubiquitin ligase, suggesting that endogenous Emi1, an apparent 44-kDa protein, requires a stabilizing factor. However, anti-Emi1 antibodies crossreact with native Emi2/Erp1/FBXO43, a homolog of Emi1 and conserved APC inhibitor. Emi2 is stable in CSF-arrested eggs, is sufficient to prevent CSF release, and is rapidly degraded in a Polo-like kinase 1-dependent manner in response to calcium-mediated egg activation. These results identify Emi2 as a candidate CSF maintenance protein.
Tung
Jeffrey J
JJ
Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Hansen
David V
DV
Ban
Kenneth H
KH
Loktev
Alexander V
AV
Summers
Matthew K
MK
Adler
John R
JR
Jackson
Peter K
PK
D000705:Anaphase / Q000502:physiology; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D020013:Calcium Signaling; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003429:Cross Reactions; D019926:Cyclin B / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008540:Meiosis / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000037:antagonists & inhibitors*; D014981:Xenopus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018797:Cell Cycle Proteins; D019926:Cyclin B; D044783:F-Box Proteins; C498166:FBXO43 protein, Xenopus; C429107:FBXO5 protein, Xenopus; D029867:Xenopus Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D017231:Proto-Oncogene Proteins c-mos