Cell Cycle: Regulation by Cyclins

Abstract The cell cycle is defined as the periodic occurrence of events that result in chromosome duplication ( deoxyribonucleic acid, DNA replication in S phase) and separation (mitosis). This process is directly regulated by both external stimuli (such as nutrient availability) and internal stimuli (such as cell size and DNA integrity). These events are co‐ordinately driven by the cyclin‐dependent kinases (CDKs) . Although the expression of CDKs typically remains relatively constant, their activities are highly regulated by CDK‐binding proteins known as Cyclins . Cyclins are structurally related proteins whose levels fluctuate throughout the cell cycle. Cyclin levels in the cell are dynamically regulated through tight control over both their rate of synthesis and degradation via ubiquitin ‐mediated proteolysis. These CDK activators also impart distinct substrate specificity to CDKs for the temporal regulation of cell division. Key Concepts: Cyclin levels oscillate throughout the cell cycle. Cyclins bind to CDKs and regulate their kinase activity. Cyclin‐CDK complexes direct the specificity of appropriate substrate interactions during the cell cycle. Inappropriate regulation of cyclins can be both the cause and the result of oncogenesis. As well as controlling normal cell cycle progression, cyclins function also in the exiting of the cell cycle (such as G0 in terminally differentiated cells and the onset of senescence caused by DNA damage).