Royal Society Publishing

Mechanisms and regulation of the degradation of cyclin B

A. Hershko


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 protein degradation in eukaryotic cells. In this pathway, proteins are targeted for degradation by ligation to ubiquitin, a process carried out by the sequential action of three enzymes: the ubiquitin–activating enzyme E1, a ubiquitin–carrier protein E2 and a ubiquitin–protein ligase E3. In the system responsible for cyclin B degradation, the E3–like function is carried out by a large complex called cyclosome or anaphase–promoting complex (APC). In the early embryonic cell cycles, the cyclosome is inactive in the interphase, but becomes active at the end of mitosis. Activation requires phosphorylation of the cyclosome/APC by protein kinase Cdk1/cyclin B. The lag kinetics of cyclosome activation may be explained by Suc1–assisted multiple phosphorylations of partly phosphorylated complex. The presence of a Fizzy/Cdc20–like protein is necessary for maximal activity of the mitotic form of cyclosome/APC in cyclin–ubiquitin ligation.