Key Concepts of Section 19.3

• Cyclin-dependent kinases are activated by cyclin subunits. Their activity is controlled at multiple levels.

• Different cyclin subunits activate CDKs at different cell cycle stages. Cyclins are present only in the cell cycle stages that they promote.

• Protein degradation is the key mechanism responsible for restricting cyclins to the appropriate cell cycle stage. This degradation is mediated by the ubiquitin-proteasome system and the ubiquitin-protein ligases APC/C and SCF.

• Activating and inhibitory phosphorylation of the CDK subunit contributes to the regulation of CDK activity.

• CDK inhibitors (CKIs) inhibit CDK activity by binding directly to the cyclin-CDK complex.

• CDKs initiate every aspect of each cell cycle stage by phosphorylating many different target proteins. Systematic efforts using protein kinases engineered to bind only modified forms of ATP have led to the identification of many of these substrates.