As mentioned in the chapter introduction, passage through the cell cycle is controlled by heterodimeric protein kinases that comprise a catalytic subunit and a regulatory subunit. The catalytic subunits, the cyclin-dependent kinases (CDKs), have no kinase activity unless they are associated with a regulatory cyclin subunit. Each CDK can associate with a small number of different cyclins, which determine the substrate specificity of the complex—that is, which proteins it phosphorylates. Each cyclin is only present and active during the cell cycle stage it promotes and hence restricts the kinase activity of the CDKs to which it binds to that cell cycle stage. Cyclin-CDK complexes activate or inhibit hundreds of proteins involved in cell cycle progression by phosphorylating them at specific regulatory sites. Thus proper progression through the cell cycle is governed by activation of the appropriate cyclin-CDK complex at the appropriate time. As we will see, restricting cyclin expression to the appropriate cell cycle stage is one of the many mechanisms cells employ to regulate the activities of each cyclin-CDK heterodimer.