Collaborative role of E2F transcriptional activity and G(1) cyclin-dependent kinase activity in the induction of S phase

A considerable body of evidence points to a role for both cyclin E/cyclin-d ependent kinase (cdk)2 activity and E2F transcription activity in the induc tion of S phase. We show that overexpression of cyclin E/cdk2 in quiescent cells induces S phase, that this coincides with an induction of E2F activit y, and that coexpression of E2F enhances the cyclin E/cdk2 mediated inducti on of S phase. Likewise, E2F overexpression can induce S phase and does so in the apparent absence of cyclin E/cdk2 activity. In addition, although th e inhibition of cyclin E/cdk2 activity blocks the induction of S phase afte r growth stimulation of normal mouse embryo fibroblasts, inhibition of cycl in E/cdk2 does not block S phase induction in Rb-/- cells where E2F activit y is deregulated. These results point to the important roles for E2F and cy clin E/cdk2 in the induction of S phase. Moreover, the nature of the E2F ta rgets and the suspected targets for cyclin E/cdk2 suggests a potential mole cular mechanism for the collaborative action of cyclin E/cdk2 and E2F in th e induction of S phase.