cyclins

Cyclins are a family of regulatory proteins that control progression through the cell cycle by activating cyclin-dependent kinases (CDKs). They do not possess intrinsic catalytic activity; upon binding to a CDK, the complex becomes a serine/threonine kinase that phosphorylates key substrates to drive cell-cycle transitions.

A given cyclin is expressed at specific times, and its levels rise and fall in a defined sequence. This cyclic abundance partners with CDK activation to regulate distinct cell-cycle phases. In many organisms, the main mammalian cyclins are Cyclin D, Cyclin E, Cyclin A, and Cyclin B. Cyclin D promotes progression through early G1, Cyclin E drives the G1/S transition, Cyclin A activity is prominent during S phase and the transition to G2, and Cyclin B governs passage into and through mitosis.

Regulation of cyclins involves transcription, translation, and targeted degradation. The proteolysis of cyclins, mainly by ubiquitin-proteasome pathways, ensures that CDK activity is transient. The anaphase-promoting complex/cyclosome (APC/C) targets cyclin B for destruction at the metaphase–anaphase transition, helping to exit mitosis. Other ubiquitin ligases also contribute to cyclin turnover at various points in the cycle.

Disruption of cyclin regulation can lead to uncontrolled cell division and is commonly associated with cancer. Because CDK activity depends on cyclin binding, changes in cyclin levels or mutations in CDKs or their inhibitors can alter cell-cycle timing. The discovery of cyclins by Tim Hunt in 1982 highlighted the periodic regulation that underpins cell division. Understanding cyclins remains central to studies of development, cancer biology, and potential therapeutic strategies targeting cell-cycle control.