Mechanisms and regulation of the degradation of cyclin B

The degradation of the cyclin B subunit of protein kinase Cdk1/cyclin B is required for inactivation of the kinase and exit from mitosis. Cyclin B is degraded by the ubiquitin pathway, a system involved in most selective prot ein degradation in eukaryotic cells. In this pathway, proteins are targeted for degradation by ligation to ubiquitin, a process carried out by the seq uential action of three enzymes: the ubiquitin-activating enzyme E1, a ubiq uitin-carrier protein E2 and a ubiquitin-protein ligase E3. In the system r esponsible for cyclin B degradation, the E3-like function is carried out by a large complex called cyclosome or anaphase-promoting complex (APC). In t he early embryonic cell cycles, the cyclosome is inactive in the interphase , but becomes active at the end of mitosis. Activation requires phosphoryla tion of the cyclosome/APC by protein kinase Cdk1/cyclin B. The lag kinetics of cyclosome activation may be explained by Suc1-assisted multiple phospho rylations of partly phosphorylated complex. The presence of a Fizzy/Cdc20-l ike protein is necessary for maximal activity of the mitotic form of cyclos ome/APC in cyclin-ubiquitin ligation.