Cyclin-dependent kinase 4, cyclin-dependent kinase 6, and cyclin-dependent kinase 8 (CDK4, CDK6, CDK8)

Cyclin-dependent kinase 4, 6, and 8 are closely related members of a kinase family that regulate cell division and transcription. CDK4 and CDK6 are activated by D-type cyclins and are essential for cell cycle progression from the G1 to S phase, primarily via phosphorylation and inactivation of retinoblastoma tumor suppressor proteins. Their dysregulation is implicated in many cancers, and selective ATP-competitive inhibitors of CDK4/6 have become important anticancer drugs, particularly in hormone receptor-positive breast cancer. CDK8, by contrast, is a Mediator complex-associated kinase regulating transcription in response to signaling cues. Unlike CDK4/6, CDK8’s activity is tightly regulated by complex formation and is a target for drugs affecting transcriptional control in cancer and other diseases.

Other names

Cell division protein kinase 4 (CDK4)Cell division protein kinase 6 (CDK6)Cyclin-dependent protein kinase 8CDK-4CDK-6CDK-8

ATP-competitive inhibition of kinase activity (CDK4/6 and CDK8 inhibitors); Blockage of retinoblastoma protein phosphorylation (CDK4/6 inhibitors); Disruption of cell cycle progression/induction of cell cycle arrest (CDK4/6 inhibitors); Inhibition of transcription regulation (CDK8 inhibitors via Mediator complex)