A CELL-CYCLE-REGULATED INHIBITOR OF CYCLIN-DEPENDENT KINASES

Cyclin-dependent kinases (Cdks) previously have been shown to drive th e major cell cycle transitions in eukaryotic organisms ranging from ye ast to humans. We report here the identification of a 28-kDa protein, p28(Ick) (inhibitor of cyclin-dependent kinase), that binds to and inh ibits the kinase activity of preformed Cdk/cyclin complexes from human cells. p28 inhibitory activity fluctuates during the cell cycle with maximal levels in G(1) and accumulates in G(1)- and G(0)-arrested cell s. These results suggest that control of the G(1)/S transition may be influenced by a family of Cdk inhibitors that include p28(Ick) and the recently described inhibitors p21(Cip1/Waf1/Cap20) and p16(Ink4).