The cdk-activating kinase (CAK): from yeast to mammals

Cell cycle progression is regulated by cyclin-dependent kinases (cdks). The activity of cdks is tightly controlled by several mechanisms, including bi nding of subunits to cdks (cyclins and inhibitors), and phosphorylation eve nts. This review focuses on the activating phosphorylation of cdks by an en zyme termed cdk-activating kinase (CAK). Two classes of CAKs have been iden tified: monomeric Cak1p from budding yeast and the p40(MO15)(cdk7)/cyclin H /MAT1 complex from vertebrates. Cak1p is the physiological CAK in budding y east and localizes to the cytoplasm. p40(MO15)(cdk7)/cyclin H/MAT1 localize s to the nucleus, is a subunit of the general transcription factor IIH and activates cdks as well as phosphorylates several components of the transcri ptional machinery. Functions, substrate specificities, regulation, localiza tion, effects on cdk structure and involvement in transcription are compare d for Cak1p and p40(MO15)(cdk7).