CDKcyclin

CDKcyclin refers to the functional complexes formed when a cyclin-dependent kinase (CDK) associates with a regulatory cyclin subunit. These holoenzymes are central drivers of the eukaryotic cell cycle and also participate in transcriptional regulation and other cellular processes. The term is used to describe the general mechanism by which CDKs achieve substrate specificity and activity through cyclin binding.

CDKs are serine/threonine kinases that are catalytically active only when bound to a cyclin. Binding relieves autoinhibition and orients the kinase active site. Activation further requires phosphorylation of the activation loop by a CDK-activating kinase (CAK). Activity is regulated by phosphorylation at inhibitory sites by Wee1 kinases and by dephosphorylation by Cdc25 phosphatases. The abundance of cyclin subunits is tightly controlled during the cell cycle, so CDK activity is temporally coordinated.

Different CDK–cyclin pairs govern progression through specific cell-cycle phases. For example, cyclin D–CDK4/6 helps drive G1 progression, cyclin E–CDK2 and cyclin A–CDK2 promote G1/S and S phase, and cyclin B–CDK1 drives entry into and progression through mitosis. Cyclin degradation, mediated by the APC/C ubiquitin ligase, contributes to mitotic exit. CKIs such as p21, p27, and the INK4 family can inhibit CDK–cyclin activity to enforce checkpoints.

Because dysregulation of CDK–cyclin activity is common in cancer, these complexes are common targets for therapeutic intervention. Small-molecule inhibitors of CDKs or modulators of cyclin expression are used in research and are being explored clinically. Studying CDK–cyclin regulation in model organisms has shed light on cell-cycle control and its integration with transcription.