Cyclin-dependent kinases (CDKs) are the core effectors of cell cycle progression. CDK activity is regulated through association with their cyclin partners and cyclin-dependent kinase inhibitors (CKIs) as well as by activating and inhibitory phosphorylation events.

Inhibition is mediated by Wee1 and Myt1 kinases that target residues at the amino terminus of CDK1. Dephosphorylation of these residues by cdc25 phosphatase leads to activation of CDK kinase activity. The CDK7/cyclinH complex is the ubiquitous mammalian CDK-activating kinase (CAK) that phosphorylates a conserved threonine residue in the T-loop domain of CDKs.

The carboxy-terminal domain of RNA polymerase II is also a target of CAK as well as CDK9/cyclinT. CDK4/6 associate with cyclinD and phosphorylate retinoblastoma protein and initiate progression through the restriction point in G1. CDK2 associates with cyclinE in early S phase and cyclinA later in G2. CDK1/cyclinB regulates the initiation of mitotic events.

(A) CDK-dependent phosphorylation disassembles the Whi5-SBF complex and leads to nuclear export of Whi5, thereby allowing SBF to recruit RNA PolII and general transcription factors (GTFs) to the promoter. MBF is likely regulated in the same fashion.

       (B) Genetic equivalence at each step in the Whi5 and Rb pathways that control G1/S transcription in yeast and mammalian cells, respectively.