PROTEOLYTIC RATCHETS THAT CONTROL PROGRESSION THROUGH MITOSIS

A key player in mitotic progression is a cell-cycle-regulated ubiquiti n-protein ligase complex known as the anaphase-promoting complex or cy closome (APC/C). The APC/C is part of the machinery that promotes the metaphase-anaphase transition by mediating the ubiquitin-dependent des truction of anaphase inhibitors and initiates exit from mitosis by deg rading mitotic cyclins. This review describes the known components and substrates of the mitotic ubiquitination machinery and discusses how a new subfamily of proteins that contain the WD40 repeat (the Fizzy/Cd c20p family) might activate the APC/C to allow temporal differences in substrate ubiquitination during progression through mitosis.