cyclinCDKs

Cyclin-dependent kinases bound to cyclins, collectively referred to as cyclin-CDKs, are a family of serine/threonine kinases that regulate the progression of the eukaryotic cell cycle and other cellular processes. The catalytic activity of a CDK depends on association with a regulatory cyclin; the pairing creates an active kinase that phosphorylates a variety of substrates to drive cell cycle transitions such as G1 to S and G2 to M, as well as processes beyond division in some organisms.

Activation and regulation of cyclin-CDKs rely on several coordinated steps. Cyclin levels rise and fall during the cell cycle, directing when CDKs are available for activation. Binding of a cyclin induces a conformational change that partially activates the CDK, but full activation typically requires phosphorylation of the activation loop (the T-loop) by a CDK-activating kinase. Inhibitory phosphorylation by kinases of the Wee1 family can temporarily block activity, while phosphatases such as Cdc25 remove these inhibitory marks to re-activate the kinase. Inhibitor proteins, including various CKIs, can bind to cyclin-CDK complexes and prevent substrate phosphorylation. Additional layers of control include transcriptional regulation of cyclins, degradation of cyclins via the ubiquitin-proteasome system, and integration with other signaling pathways.

Across eukaryotes, different cyclin-CDK partnerships govern distinct cell cycle stages. In mammals, for example, CDK4/6 pair with cyclin D to promote G1 progression, CDK2 with cyclin E/A to drive G1/S and S phases, and CDK1 with cyclin B to trigger mitosis; yeast and plants use analogous but sometimes divergent cyclin-CDK combinations. Beyond cell division, certain cyclin-CDKs participate in transcription, differentiation, and development.

Dysregulation of cyclin-CDKs is a hallmark of many cancers, leading to unchecked proliferation. Consequently, CDK inhibitors and related therapeutic strategies aim to restore cell cycle control by targeting cyclin-CDK activity, highlighting the central role of these complexes in cellular homeostasis and disease.