CDK6

CDK6 (cyclin-dependent kinase 6) is a serine/threonine kinase in the cyclin-dependent kinase family that regulates cell cycle progression and other cellular processes. It forms active complexes with D-type cyclins (D1, D2, and D3) and, after activation by phosphorylation, targets substrates involved in transitioning from G1 to S phase.

In the G1/S transition, CDK6–cyclin D complexes phosphorylate the retinoblastoma protein (RB1) and related pocket proteins. This phosphorylation releases E2F transcription factors, enabling transcription of S-phase genes and DNA synthesis. Beyond RB1 phosphorylation, CDK6 is thought to participate in transcriptional regulation and chromatin-related processes in certain contexts, with roles noted in development and hematopoiesis.

CDK6 is expressed in proliferating tissues and is frequently upregulated in cancers, where its activity supports sustained cell proliferation. Genetic or epigenetic alteration of CDK6 has been observed in various malignancies, and in some tumors CDK6 helps maintain the proliferative state. The activity of CDK6 is regulated by cyclin binding and by inhibitors of the INK4 family, such as p16INK4a, which prevent activation of CDK4/6.

Therapeutically, selective inhibitors targeting CDK4/6, including palbociclib, ribociclib, and abemaciclib, are approved for certain breast cancers and are being evaluated in other malignancies. These drugs reduce RB1 phosphorylation, reinforcing G1 arrest and limiting cell proliferation. CDK6 remains a focus of research for understanding cell cycle control and developing cancer therapies.