Cyclin-dependent kinase 4, Cyclin-dependent kinase 6, and Cyclin-dependent kinase 9 (CDK4, CDK6, CDK9)

Cyclin-dependent kinases 4, 6, and 9 (CDK4, CDK6, CDK9) are serine/threonine kinases that regulate critical cellular processes. CDK4 and CDK6 are essential for driving the cell cycle from the G1 to S phase by phosphorylating the retinoblastoma protein (RB), thus enabling DNA replication and cell division[1][2][3][4][5][6][7][8]. They function as catalytic subunits, activated by D-type cyclins, and their dysregulation is strongly implicated in cancer, leading to the development and clinical use of selective CDK4/6 inhibitors especially in breast cancer[3][4][6][7]. CDK9 primarily regulates transcriptional elongation by phosphorylating the RNA polymerase II C-terminal domain, governing gene expression including those involved in cell survival (such as anti-apoptotic proteins)[3]. Aberrant activity of CDK9 is associated with cancer and viral replication. All three kinases serve as validated therapeutic targets, and their inhibition is the strategy behind several anti-cancer drugs in clinical use.

Other names

CDK4: Cell division protein kinase 4CDK6: Cell division protein kinase 6CDK9: Positive transcription elongation factor b catalytic subunitCDK9: P-TEFb kinaseCDK9: sometimes referred to as TAK or CDC2L4Collective: CDK4/6 (for CDK4 and CDK6, when discussed together in cell cycle or cancer context)Collective: CDKs (generic)

Inhibitors block kinase activity, resulting in cell cycle arrest at G1/S (CDK4/6 inhibitors) or suppression of transcriptional elongation and anti-apoptotic gene expression (CDK9 inhibitors) Prevent phosphorylation of retinoblastoma protein (CDK4/6) Suppress RNA polymerase II phosphorylation (CDK9)