Cell cycle progression is controlled in part by a family of cyclin proteins and cyclin dependent kinases (Cdks). Cdk proteins work in concert with the cyclins to phosphorylate key substrates involved in each phase of cell cycle progression. Another family of proteins, Cdk inhibitors, also plays a role in regulating the cell cycle by binding to cyclin-Cdk complexes and modulating their activity. Several Cdk proteins have been identified, including Cdk2-Cdk8, PCTAIRE-1-PCTAIRE-3, PITALRE and PITSLRE. Cdk6 is known to associate with cyclins D1, D2 and D3 and to be involved with the G1/S transition of the cell cycle. Multiple inhibitors of Cdk6 have been identified, including p18 and p19. These inhibitors bind to both free and complexed Cdk6, and they inhibit the activity of the cyclin D-bound Cdk6.