A Cell Cycle-Regulated Inhibitor of Cyclin-Dependent Kinases

Cyclin-dependent kinases (Cdks) previously have been shown to drive the major cell cycle transitions in eukaryotic organisms ranging from yeast to humans. We report here the identification of a 28-kDa protein, p28Ick(inhibitor of cyclin-dependent kinase), that binds to and inhibits the kinase activity of preformed Cdk/cyclin complexes from human cells. p28 inhibitory activity fluctuates during the cell cycle with maximal levels in G1and accumulates in G1- and G0-arrested cells. These results suggest that control of the G1/S transition may be influenced by a family of Cdk inhibitors that include p28Ickand the recently described inhibitors p21Cip1/Waf1/Cap20and p16Ink4.