Progression through the cell cycle requires activation of a series of enzymes designated cyclin dependent kinases (Cdks). The monomeric catalytic subunit, Cdk2, a critical enzyme for initiation of cell cycle progression, is completely inactive. Partial activation is achieved by the binding of regulatory cyclins such as cyclin D1, while full activation requires, in addition, phosphorylation at Thr-160. The enzyme responsible for phosphorylation of Thr-160 in Cdk2 and also Thr-161 in Cdc2 p34, designated Cdk-activating kinase (CAK), has been partially purified and shown to be comprised of a catalytic subunit and a regulatory subunit. The catalytic subunit, designated Cdk7, has been identified as the mammalian homolog of MO15, a protein kinase demonstrated earlier in starfish and Xenopus. The regulatory subunit is a novel cyclin (cyclin H) and is required for activation of Cdk7. Like other Cdks, Cdk7 contains a conserved threonine required for full activity; mutation of this residue severely reduces CAK activity.
