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 G1 and 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 p28Ick and the recently described inhibitors p21Cip1/Waf1/Cap20 and p16Ink4.
Hengst
L
L
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Dulic
V
V
Slingerland
J M
JM
Lees
E
E
Reed
S I
SI
D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases
D016213:Cyclins; D047428:Protein Kinase Inhibitors; D008148:Lovastatin; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases