Cyclins and Cyclin-Dependent Kinases: Theme and Variations

Abstract

Publisher Summary This chapter introduces cyclins and their partner—cyclin dependent kinases (CDKs)—and the ways in which CDK complexes can be regulated. Cyclins are intimately concerned with regulating and coordinating deoxyribonucleic acid (DNA) replication and cell division. As more and more diverse cyclins and their partner CDKs are identified, more and more cellular processes are likely to be found to be regulated by these highly flexible protein kinase complexes. The cell cycle describes the series of steps by which a cell coordinates the processes of DNA duplication and cell division and is generally divided into four phases: cell division (M phase), the first gap phase (G1), DNA replication (S phase), and the second gap phase (G2). The cell cycle proceeds via a number of “control points.” These are points at which cells monitor the correct completion of a process—such as DNA replication—and whether conditions are favorable to go on to the next stage. To be activated fully, the CDK component of the cyclin–CDK complex needs to be phosphorylated on a conserved threonine in the T loop. There are a variety of inhibitor proteins that bind specifically to the CDKs and inhibit them in a stoichiometric fashion. Start, which is the major cell-cycle control point in most somatic cells, is described in the chapter. At start, there is a clear interaction between the cyclin–CDK complexes. In mammalian cells, the approximate equivalent to start is the restriction point (R), and the D-type cyclins are most likely to be involved in its regulation.