Cyclin-dependent kinase 2, Cyclin-dependent kinase 7, Cyclin-dependent kinase 9 (CDK2, CDK7, CDK9)

Cyclin-dependent kinases 2, 7, and 9 are serine/threonine protein kinases that require association with regulatory cyclins for activation. CDK2 primarily regulates the G1/S cell cycle transition and DNA synthesis. CDK7 is a dual-function kinase, serving both as a CDK-activating kinase (CAK), which phosphorylates and activates CDK1, CDK2, CDK4, and CDK6 to regulate cell cycle progression, and as a pivotal regulator of RNA polymerase II-mediated transcription via the TFIIH complex. CDK9 is a central transcriptional CDK that, together with its cyclin partners, catalyzes phosphorylation of RNA polymerase II, thereby regulating transcriptional elongation—an activity exploited by many cancers for rapid gene expression. All three kinases are established therapeutic targets, particularly in oncology, owing to their roles in cell division and gene expression; numerous small-molecule inhibitors are clinically explored or used[1][3][6][5][2][4][7][9].

Other names

p33(CDK2)cyclin-dependent kinase 2CDK-activating kinase catalytic subunit (CAK)MO15PITALREcyclin-dependent kinase 9CDK9~42~CDK9~55~

Inhibition of CDK2 leads to cell cycle arrest in G1/S transition, blocking DNA synthesis. Inhibition of CDK7 impairs both cell cycle progression and Pol II-dependent transcription initiation. Inhibition of CDK9 halts transcriptional elongation by preventing phosphorylation of the CTD domain of RNA polymerase II, reducing short-lived anti-apoptotic protein expression.