CDKs are regulated through multiple mechanisms to ensure precise cell cycle control:
1. Cyclin Binding: Cyclins are essential for CDK activation. The binding of cyclins to CDKs not only activates the kinases but also determines their substrate specificity. 2. Phosphorylation and Dephosphorylation: CDKs themselves undergo phosphorylation at specific residues, which can either activate or inhibit their activity. For example, CDK1 is activated by phosphorylation at Thr161 and inhibited by phosphorylation at Tyr15. 3. CDK Inhibitors: Proteins such as p21, p27, and p16 can bind to CDKs or cyclin-CDK complexes, inhibiting their kinase activity and thereby halting cell cycle progression.