APC/C–Cdc20-mediated degradation of cyclin B participates in CSF arrest in unfertilized Xenopus eggs

• Published in: Developmental biology Vol. 279; no. 2; pp. 345 - 355
• Main Authors: Yamamoto, Tomomi M., Iwabuchi, Mari, Ohsumi, Keita, Kishimoto, Takeo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2005
• Subjects: Anaphase-Promoting Complex-Cyclosome; Animals; CDC2 Protein Kinase - metabolism; Cdc20; Cell Cycle - physiology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cyclin B - genetics; Cyclin B - metabolism; Cyclin B degradation; Cytostatic factor; MAP kinase; MAP Kinase Signaling System - physiology; Metaphase II arrest; Mos; Ovum - cytology; Ovum - physiology; Proto-Oncogene Proteins c-mos - genetics; Proto-Oncogene Proteins c-mos - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; The anaphase-promoting complex/cyclosome; Ubiquitin-Protein Ligase Complexes - genetics; Ubiquitin-Protein Ligase Complexes - metabolism; Xenopus egg; Xenopus laevis; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Mos; Xenopus egg; The anaphase-promoting complex/cyclosome; Cytostatic factor; Cyclin B degradation; MAP kinase; Metaphase II arrest; Cdc20
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2004.12.025

In vertebrates, unfertilized eggs are arrested at meiotic metaphase II (meta-II) by cytostatic factor (CSF), with Cdc2 activity maintained at a constant, high level. CSF is thought to suppress cyclin B degradation through the inhibition of the anaphase-promoting complex/cyclosome (APC/C)-Cdc20 while cyclin B synthesis continues in unfertilized eggs. Thus, it is a mystery how Cdc2 activity is kept constant during CSF arrest. Here, we show that the APC/C–Cdc20 can mediate cyclin B degradation in CSF-arrested Xenopus eggs and extracts, in such a way that when Cdc2 activity is elevated beyond a critical level, APC/C–Cdc20-dependent cyclin B degradation is activated and Cdc2 activity consequently declines to the critical level. This feedback control of Cdc2 activity is shown to be required for keeping Cdc2 activity constant during meta-II arrest. We have also shown that Mos/MAPK pathway is essential for preventing the cyclin B degradation from inactivating Cdc2 below the critical level required to sustain meta-II arrest. Our results indicate that under CSF arrest, Mos/MAPK activity suppresses cyclin B degradation, preventing Cdc2 activity from falling below normal meta-II levels, whereas activation of APC/C–Cdc20-mediated cyclin B degradation at elevated levels of Cdc2 activity prevents Cdc2 activity from reaching excessively high levels.