The cyclin-dependent protein kinases and the control of cell division.

A few years after the identification of cyclin B-cdc2 kinase as the universal factor that controls onset of M-phase in eukaryotic cells, MPF (M-phase promoting factor), it became evident that all transitions of the cell cycle are controlled through phosphorylation of specific targets due to changes in the activity of a variety of cyclin-dependent kinases (cdks). These transitions include conversion of quiescent cells to a state of active proliferation, commitment to DNA replication, initiation of DNA replication, and entry into and exit from mitosis. Changes in the activity of cdks along the cell cycle depend not only on their association with a variety of cyclins (including G1/S and G2/M cyclins) and on posttranslational modifications by phosphorylation-dephosphorylation reactions, but also on specific protein inhibitors and on protein degradation.