Cyclin-dependent kinase 6 (CDK6)

Cyclin-dependent kinase 6 (CDK6) is a serine/threonine protein kinase encoded by the CDK6 gene located on chromosome 7q21.2. It is approximately 36.9 kDa and contains a catalytic core, an ATP-binding pocket, regulatory phosphorylation sites, a cyclin-binding domain, and an activating T-loop. CDK6 plays a crucial role in cell cycle regulation, particularly G1 phase progression and the G1/S transition, by forming complexes with D-type cyclins (D1, D2, D3) and phosphorylating the retinoblastoma protein (pRB) to release E2F transcription factors. Its activity is regulated by D-type cyclins, INK4 family inhibitors, Cip/Kip proteins, and phosphorylation events. CDK6 is found in both the cytoplasm and nucleus, with active complexes predominantly nuclear. Deregulation and overexpression are linked to various cancers, making it a therapeutic target for which inhibitors like palbociclib, ribociclib, and abemaciclib exist.

Other names

Cell division protein kinase 6Serine/threonine-protein kinase PLSTIRECDKN6CR2 protein kinaseCRK2

CDK6 inhibitors work by blocking the phosphorylation of retinoblastoma protein (Rb), preventing the release of E2F transcription factors, inhibiting cell cycle progression at the G1/S transition, and inducing cell cycle arrest.