Cyclin-Dependent Kinases and Cyclin-Dependent Kinase Inhibitors.

Normal cellular proliferation is under the tight control of both positive and negative regulators that determine whether a particular cell can progress through the cell cycle (seerefs. 1-3 for reviews). This carefully ordered progression of the mammalian cell cycle is controlled by the sequential formation, activation, and deactivation of specific cell cycle-regulatory molecules (Fig. 1) that exist as a series of complexes consisting of a catalytic kinase subunit (known as the cyclin-dependent kinase or CDK) and a regulatory cyclin subunit. These cyclin:CDK complexes form part of the positive regulatory machinery that drives the cell through the cycle. Most cyclin mRNAs and proteins show a dramatic fluctuation in their expression during the cell cycle. For example,G1/s cyclin, cyclin, cyclin E is unstable, peaks during lateG1 and disappears rapidly thereafter, whereas cyclins A and B accumulate transiently at the onset of S phase and in late G2 respectively, followed by their rapid degradation (1,2). In contrast, expression of the various CDK molecules remains relatively constant throughout the cell cycle. [ABSTRACT FROM AUTHOR]