Figure 1.

Cyclin-dependent kinases (CDKs) and their cyclin regulatory subunits. CDK-cyclin complexes with direct functions in regulating the cell cycle. CDK3/cyclin C drives cell cycle entry from G0. CDK4/6/cyclin D complexes initiate phosphorylation of the retinoblastoma protein (pRb) and they sequester p21^Cip1 and p27^kip1 (not shown), which are both inhibitors of CDK2, thus promoting the activation of CDK2/cyclin E complex. In late G1, CDK2/cyclin E complex completes phosphorylation and inactivation of pRb, which releases the E2F transcription factors and G1/S transition takes place. DNA replication takes place in S phase. CDK2/cyclin A complex regulates progression through S phase and CDK1/cyclin A complex through G2 phase in preparation for mitosis (M). Mitosis is initiated by CDK1/cyclin B complex. The activity of CDK1/cyclin B is tightly regulated by activating phosphorylation by the CDK-activating kinase CAK (a heterodimer of cyclin H-CDK7-MAT1) and inhibitory phosphorylations by Wee1 and Myt1 on Tyr15 and Thr14 (not shown). The specific CDK4/CDK6 pharmacological inhibitors described in this study are shown.