CYCLIN-DEPENDENT PROTEIN-KINASES - KEY REGULATORS OF THE EUKARYOTIC CELL-CYCLE

Passage through the cell cycle requires the successive activation of d ifferent cyclin-dependent protein kinases (CDKs). These enzymes are co ntrolled by transient associations with cyclin regulatory subunits, bi nding of inhibitory polypeptides and reversible phosphorylation reacti ons. To promote progression towards DNA replication, CDK/cyclin comple xes phosphorylate proteins required for the activation of genes involv ed in DNA synthesis, as well as components of the DNA replication mach inery. Subsequently, a different set of CDK/cyclin complexes triggers the phosphorylation of numerous proteins to promote the profound struc tural reorganizations that accompany the entry of cells into mitosis. At present, much research is focused on elucidating the links between CDK/cyclin complexes and signal transduction pathways controlling cell growth, differentiation and death. In future, a better understanding of the cell cycle machinery and its deregulation during oncogenesis ma y provide novel opportunities for the diagnostic and therapeutic manag ement of cancer and other proliferation-related diseases.