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. Cyclin-dependent kinase activity is regulated by T-loop phosphorylation (Thr172 in the case of CDK4), by the abundance of their cyclin partners, and by association with CDK inhibitors of the Cip/Kip or INK family of proteins Cdk4, in complex with D-type cyclins, is thought to regulate cell growth during the G1 phase of the cell cycle. This association with a D-type cyclin upregulates Cdk4 activity, whereas binding to the Cdk inhibitor p16 downregulates Cdk4 activity.