CDK2 (cyclin-dependent kinase 2), a serine/threonine protein kinase, is the catalytic subunit of the heterodimeric cyclin-dependent kinase complex required for G1/S phase transition. The kinase activity of CDK2 is regulated by the association with a cyclin subunit, CDK inhibitors, and its phosphorylation state. The active CDK2/cyclin A complex interacts with the N-terminus of E2F-1 and directs the phosphorylation of E2F-1 and DP-1. The active CDK2/cyclin E complex phosphorylates Rb which disrupts its binding to E2F, allowing E2F activation and transcription of the genes necessary for S-phase entry and progression. Inhibition of the CDK2/cyclin complex can be attributed to its association with p21Waf1/Cip1 and p27Kip1 and the phosphorylation of CDK2 on Thr14 and Tyr15. The activation of the CDK2/cyclin complex requires the phosphorylation of Thr160 and the dephosphorylation of Tyr14 and Tyr15.