Cyclin-dependent kinase 6 (CDK6)

Cyclin-dependent kinase 6 Overview

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.

Mechanism of Action

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.

Biological Functions

Safety Considerations

Interacting Drugs

Associated Biomarkers