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

Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are closely related serine/threonine kinases that function as key regulators of cell cycle progression, specifically controlling the transition from G1 to S phase by forming complexes with D-type cyclins (D1, D2, D3)[1][2][3][4][5]. These complexes phosphorylate the retinoblastoma (Rb) protein, releasing E2F transcription factors and promoting S phase entry[3][4][5]. Dysregulation, overexpression, or genetic alterations of CDK4/6 pathways are frequent in human cancers, and pharmacological inhibition of CDK4/6 is approved for the treatment of hormone receptor-positive, HER2-negative advanced breast cancer; clinical applications in other malignancies are under study[4][5][6]. Both CDK4 and CDK6 are regulated by cyclins, CDK inhibitors (especially the INK4 and Cip/Kip families), and mitogenic signaling[3][5]. Their inhibition leads to a potent antiproliferative effect in tumor cells reliant on this cell cycle transition[5][6].

Other names

cell division protein kinase 4 (for CDK4)cell division protein kinase 6 (for CDK6)CDK4/6 (referring to both kinases collectively)

Inhibition of CDK4/6, preventing phosphorylation of retinoblastoma protein (Rb); Induction of cell cycle arrest at G1 phase