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Regulation of cell proliferation is a complex process involving the regulated expression and/or modification of discrete gene products, which control transition between different stages of the cell cycle. The purpose of this short review is to provide an overview of somatic cell cycle events and their controls. Cyclins have appeared as major positive regulators in this network, because their association to the cyclin-dependent kinases (Cdks) allows the subsequent activation of the C아/cyclin complexes and their catalatic activity. In mammalian cells, early to mid G1 progression and late G1 progression leading to S phase entry are directed by D-type cyclins-Cdk4, 6 and cyclin E-C아2 both of which can phosphorylate the retinoblastoma protein (pRB). pRB, is a transcriptional repressor which, in its unphosphorylate state, binds to members of the E2F transcription factor family and blocks E2F-dependent transcription of genes controlling the G1 to S phase transition and subsequent DNA synthesis. Cyclin A is produced in late G1 and expressed during S and G2 phase, and expression of B-type cyclins is typically maximal during the G2 to M phase transition and it controls the passage through M phase. They primarily associate with and activate Cdk2, and Cdc2, respectively. On the other hand, the Cdk inhibitors negatively control the activity of Cdk/cyclin complex by coordinating internal and/or external signals and impending proliferation at several key checkpoints. These current and further findings will provide novel approaches t understanding and treating major diseases.
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