HOW PROTEOLYSIS DRIVES THE CELL-CYCLE

Oscillations in the activity of cyclin-dependent kinases (CDKs) promot e progression through the eukaryotic cell cycle. This review examines how proteolysis regulates CDK activity-by degrading CDK activators or inhibitors-and also how proteolysis may directly trigger the transitio n from metaphase to anaphase; Proteolysis during the cell cycle is med iated by two distinct ubiquitin-conjugation pathways. One pathway, req uiring CDC34, initiates DNA replication by degrading a CaK inhibitor, The second pathway, involving a large protein complex called the anaph ase-promoting complex or cyclosome, initiates chromosome segregation a nd exit from mitosis by degrading anaphase inhibitors and mitotic cycl ins, Proteolysis therefore drives cell cycle progression not only by r egulating CDK activity, but by directly influencing chromosome and spi ndle dynamics.