Cyclin-dependent kinase (CDK) and cyclin complex (CDK/Cyclin)

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that require association with regulatory subunits called cyclins to become catalytically active. These complexes serve as central regulators of the eukaryotic cell cycle, orchestrating the transition between different phases (G1, S, G2, and M) through the phosphorylation of key substrates such as the retinoblastoma (Rb) protein [Malumbres M. Genome Biol. 2014;15(6):122]. Beyond cell cycle control, specific CDK/cyclin pairs, such as CDK7 and CDK9, are involved in regulating transcription by phosphorylating the RNA polymerase II C-terminal domain [Sanchez-Martinez C, et al. Bioorg Med Chem Lett. 2015;25(17):3420-3435]. Dysregulation of the CDK/cyclin axis, often through cyclin D1 overexpression or loss of endogenous inhibitors like p16INK4a, is a hallmark of many cancers, leading to uncontrolled cell proliferation [Asghar U, et al. Nat Rev Drug Discov. 2015;14(2):130-146]. Consequently, CDKs have become major therapeutic targets, with several selective CDK4/6 inhibitors approved for treating hormone receptor-positive, HER2-negative breast cancer [Spring LM, et al. JAMA Oncol. 2020;6(8):1231-1238]. While early pan-CDK inhibitors faced challenges due to narrow therapeutic windows and off-target toxicity, modern selective inhibitors have demonstrated significant clinical efficacy by inducing cell cycle arrest and enhancing anti-tumor immune responses [Otto T, Sicinski P. Nat Rev Cancer. 2017;17(2):93-115]. In addition to oncology, CDKs are being investigated for their roles in neurodegeneration and viral replication, suggesting a broader therapeutic potential for CDK inhibitors in the future [Asghar U, et al. Nat Rev Drug Discov. 2015;14(2):130-146].

Other names

CDKsCyclin-dependent serine/threonine kinasesCell cycle kinasesCDK-cyclin complex

ATP-competitive inhibition of the CDK catalytic subunit, preventing the formation of an active complex with cyclins and subsequent phosphorylation of downstream targets like the retinoblastoma (Rb) protein, leading to cell cycle arrest [PubMed: 25594219].