Cell Cycle

             Key regulators in G1 phase progression:.
             The entry of the cell into the G1 phase of the cell cycle is stimulated by extracellular signals. Once the cells are stimulated to enter the cycle from a nondividing stage(G0), cyclins and cyclin dependent kinases are called into action.
             Cyclins are proteins that serve to bind and activate cyclin dependent kinases. Cyclins also direct activated cyclin dependent kinases to specific substrates in the cell cycle, allowing different cyclins to promote different cell cycle events. Two of the four classes of cyclins involved in G1 phase are the G1 cyclins and G1/s cyclins. It is thought that G1 cyclins, D cyclins, senses cell growth and couples this growth with entry into a new cycle. G1/S cyclins, Cyclin E, function in initiating the processes leading to DNA replication by acting to relieve the braking systems that suppress kinase activity in the S phase of the cell cycle. Cyclins have a tertiary structure made up of a core of two compact domains each of which contain five alpha helices. The first five helix bundles correspond to the cyclin box. In the amino terminal region there are regulatory and targeting domains that are specific for each cyclin. Cyclin dependent kinases interact with the first helical bundle and with the N terminal helix.
             Cyclin dependent kinases are protein kinases that are activated when bound to cyclins. Eukaryotic cells have at least nine cyclin dependent kinases, four of which are involved in cell cycle control, three are involved in cell cycle progression. Cyclin dependent kinases 4 and 6 complex with cyclin D and triggers the phosphorylation of an important factor in the Rb pathway. This factor sets off a cascade of events which culminate with the induction of the G1/S cyclin, cyclin E, which activates cyclin dependent kinase 2. The Cyclin E- CDK2 complex assists the cyclin D dependent kinases in phosphorylating the factor in the Rb pathway.