Cyclin-dependent kinase 2–cyclin E complex or cyclin-dependent kinase 2–cyclin A complex (CDK2–cyclin E, CDK2–cyclin A)

The CDK2–cyclin E and CDK2–cyclin A complexes are central regulators of the eukaryotic cell cycle, mediating critical transitions from the G1 phase into S phase and driving DNA replication. CDK2 must bind to either cyclin E (late G1 to S phase) or cyclin A (during S phase) to become activated. This activation typically requires phosphorylation of CDK2 at Thr160 by an upstream CDK-activating kinase. Once activated, the complexes phosphorylate key substrates such as the retinoblastoma protein (RB), E2F family transcription factors, and other proteins involved in DNA synthesis, repair, and centrosome duplication. Dysregulation of cyclin E/A–CDK2 activity is strongly associated with tumorigenesis—resulting in unscheduled replication, genomic instability, and resistance to cell cycle checkpoints. Both complexes are major research and therapeutic targets in cancer and are commonly interrogated in drug development and biomarker analysis[1][3][4][5][8].

Other names

CDK2–cyclin E complexCDK2–cyclin A complexCdk2/ECdk2/ACyclin-dependent kinase 2–cyclin ECyclin-dependent kinase 2–cyclin ACell division protein kinase 2–cyclin ECell division protein kinase 2–cyclin A

Inhibition of CDK2 kinase activity, leading to cell cycle arrest (G1 or S phase) and apoptosis in dividing cells Disruption of cyclin–CDK binding, preventing CDK2 activation and substrate phosphorylation