Cyclin-dependent kinase 2–Cyclin A complex (CDK2–Cyclin A)

The Cyclin-dependent kinase 2–Cyclin A complex (CDK2–Cyclin A) is a heterodimeric serine/threonine kinase that plays a pivotal role in the orchestration of the eukaryotic cell cycle (UniProt P24941, P20248). It is primarily active during the S phase, where it facilitates DNA replication, and the G2 phase, where it prepares the cell for entry into mitosis (PubMed: 10523320). The complex functions by phosphorylating key substrates such as the retinoblastoma protein (Rb) and E2F transcription factors, which are essential for the expression of genes required for cell cycle progression (StatPearls: Cyclin Dependent Kinase). In various malignancies, including breast and lung cancers, the Cyclin A–CDK2 complex is frequently overexpressed, driving aberrant proliferation and contributing to therapeutic resistance (PubMed: 26912533). Therapeutic strategies targeting this complex involve small-molecule inhibitors like Dinaciclib and Seliciclib, which compete with ATP for the binding pocket of CDK2 to block its enzymatic activity (PubChem: Dinaciclib). While effective in preclinical models, the clinical application of these inhibitors faces challenges such as dose-limiting toxicities like myelosuppression and the need for precise biomarkers to identify responsive patient populations (ClinicalTrials.gov).

Other names

Cyclin A2-CDK2 complexCCNA2-CDK2Cyclin A-CDK2CDK2-CCNA2

Competitive inhibition of the ATP-binding site on the CDK2 subunit, which prevents the phosphorylation of downstream substrates such as the retinoblastoma protein (Rb) and E2F, thereby halting cell cycle progression in the S and G2 phases (PubChem; PubMed: 10523320).