cyclinCDK

Cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases that, when bound to a regulatory cyclin subunit, drive progression through the eukaryotic cell cycle and coordinate other cellular processes. The complex formed by a CDK and its cyclin—often called a cyclin-CDK complex—exhibits kinase activity only when the cyclin partner is present, which provides substrate specificity and timing. Activation typically requires phosphorylation of the CDK by a CDK-activating kinase (CAK) and relief of autoinhibition, as well as removal of inhibitory phosphates by phosphatases such as Cdc25. Cyclin levels rise and fall during the cell cycle, ensuring the orderly sequence of events.

Regulation of cyclin-CDK activity involves multiple layers. Cyclin synthesis and targeted destruction by the ubiquitin–proteasome system tightly control when each complex is active. In addition, CDK inhibitors (CKIs) can block activity, and post-translational modifications modulate kinase function. Localization and degradation of cyclins help ensure that CDK activity is restricted to appropriate cell-cycle stages.

In humans, distinct cyclin-CDK pairs govern major cell-cycle transitions: Cyclin D–CDK4/6 promotes G1 progression and Rb phosphorylation; Cyclin E–CDK2 drives the G1/S transition; Cyclin A–CDK2 participates in S phase; Cyclin B–CDK1 drives the G2/M transition. Beyond cell cycle control, cyclin-CDKs participate in transcriptional regulation and DNA repair. Dysregulation is common in cancer, and selective CDK inhibitors (e.g., palbociclib, ribociclib, abemaciclib) targeting CDK4/6 have become important cancer therapies. The cyclin-CDK system is evolutionarily conserved, though organismal diversity yields different sets of cyclins and CDKs with some functional redundancy.