cyclinCDKkomplex

The cyclin-dependent kinase (CDK) complexes are protein kinases that play a critical role in regulating the cell cycle, a tightly controlled process that ensures proper cell division and proliferation. These complexes are composed of two main components: a catalytic subunit known as a cyclin-dependent kinase (CDK) and a regulatory subunit called a cyclin. The combination of CDKs with cyclins forms active CDK-cyclin complexes, which phosphorylate target proteins to drive progression through distinct phases of the cell cycle.

CDKs are conserved across eukaryotes, with homologs found in yeast, plants, and animals. The human genome encodes approximately 20 CDKs, though only a subset—including CDK1, CDK2, CDK4, CDK6, and CDK7—are directly involved in cell cycle regulation. Cyclins, named for their fluctuating levels during the cell cycle, bind to CDKs to activate them. The activity of CDK-cyclin complexes is further modulated by phosphorylation and dephosphorylation events, as well as inhibitory proteins such as CDK inhibitors (CKIs), which include p21, p27, and p57.

The cell cycle consists of interphase (G1, S, and G2 phases) and mitosis (M phase). CDK-cyclin complexes drive transitions between these stages:

- **G1 phase**: CDK4/6-cyclin D complexes promote progression from G1 to S phase by phosphorylating the retinoblastoma protein (Rb), releasing E2F transcription factors that activate genes required for DNA synthesis.

- **S phase**: CDK2-cyclin E and CDK2-cyclin A complexes facilitate DNA replication by phosphorylating proteins involved in DNA synthesis and checkpoint control.

- **G2/M transition**: CDK1-cyclin B complexes activate at the G2/M checkpoint, preparing the cell for mitosis.

- **Mitosis**: CDK1-cyclin B remains active during M phase, coordinating chromosome condensation, spindle formation, and sister chromatid separation.

Disruptions in CDK-cyclin regulation can lead to uncontrolled cell proliferation, contributing to cancer development. Targeting CDKs with small-molecule inhibitors is an active area of research in oncology, aiming to disrupt malignant cell cycles while sparing normal cells. Proper functioning of these complexes is also essential for developmental processes, tissue homeostasis, and responses to cellular stress.