Cyclin

Cyclins are a family of regulatory proteins that control progression through the eukaryotic cell cycle by activating cyclin-dependent kinases (CDKs). Their levels rise and fall in a cell-cycle–dependent manner, enabling orderly transitions between phases.

In mammals, cyclins are commonly grouped into four main types: D-type (G1 phase and response to mitogenic signals), E-type (G1/S transition), A-type (S phase and G2), and B-type (mitosis). Yeast and other organisms have analogous families, such as CLN and CLB, that perform similar regulatory roles. The precise combination of cyclin and CDK determines the substrate specificity and timing of phosphorylation events.

Mechanism and regulation: Cyclins bind to CDKs to form active kinase complexes that phosphorylate target proteins, driving cell-cycle events such as DNA replication, chromosome segregation, and mitotic entry. Activation involves conformational changes and sometimes dephosphorylation of inhibitory sites; CDK activity is further regulated by phosphorylation via kinases like Wee1 and dephosphorylation by Cdc25. Cyclins are themselves tightly controlled by synthesis and targeted destruction. Ubiquitin ligases of the SCF and APC/C families mark specific cyclins for degradation at defined cell-cycle points, resetting the system. Inhibitory proteins, known as CDK inhibitors (CKIs) such as p21, p27, and p16, can block cyclin-CDK activity.

Biological significance: Proper cyclin-CDK activity is essential for accurate cell-cycle progression. Dysregulation of cyclins or CDKs is linked to cancer and developmental disorders. Cyclins are explored as therapeutic targets, with CDK inhibitors used to modulate cell proliferation in certain cancers. Evolutionarily, cyclins are conserved across eukaryotes, with diverse family members arising from gene duplication to support complex regulation in multicellular organisms.