Cyclin-dependent kinase 3, 4, 5, 6, 14, and 16 (CDK3-6/14/16)

CDK3-6 and cyclin Y-associated CDKs (primarily CDK14 and CDK16) constitute a subset of the cyclin-dependent kinase family that regulates critical aspects of the cell cycle and intracellular signaling. CDK4 and CDK6 are well-established drivers of the G1-to-S phase transition through the phosphorylation of the retinoblastoma protein (Rb), and their inhibition is a cornerstone of modern breast cancer therapy. CDK3 and CDK5 contribute to cell cycle entry from quiescence and neuronal development, respectively, while the cyclin Y-associated kinases CDK14 and CDK16 are membrane-localized regulators of the Wnt signaling pathway and autophagy. Dysregulation of these kinases, often through gene amplification or cyclin overexpression, is a common feature in various malignancies, including breast, lung, and hepatocellular carcinomas. While first-generation CDK inhibitors were relatively non-selective, newer agents like abemaciclib exhibit a broader inhibitory profile that includes these atypical CDKs, potentially enhancing efficacy but also influencing the safety profile. Understanding the collective role of these kinases is essential for developing next-generation therapies that can overcome resistance to selective CDK4/6 inhibition.

Other names

CDK3CDK4CDK5CDK6CDK14CDK16PFTK1PCTK1Cell cycle-associated CDKsCyclin Y-associated kinasesPFTAIRE1PCTAIRE1

ATP-competitive inhibition of the kinase domain, preventing the phosphorylation of downstream substrates such as the retinoblastoma protein (Rb) and LRP6, thereby inducing cell cycle arrest and inhibiting oncogenic signaling pathways.