Cyclin A is a mediator of p120(E4F)-dependent cell cycle arrest in G(1)

E4F is a ubiquitously expressed GLI-Kruppel-related transcription factor wh ich has been identified for its capacity to regulate transcription of the a denovirus E4 gene in response to Elk However, cellular genes regulated by E 4F are still unknown. Some of these genes are likely to be involved in cell cycle progression since ectopic p120(E4F) expression induces cell cycle ar rest in G(1). Although p21(WAF1) stabilization was proposed to mediate E4F- dependent cell cycle arrest, we found that p120(E4F) can induce a G(1) bloc k in p21(-/-) cells, suggesting that other proteins are essential for the p 120(E4F)-dependent block in C-1. We show here that cyclin A promoter activi ty can be repressed by p120(E4F) and that this repression correlates with p 120(E4F) binding to the cyclic AMP-responsive element site of the cyclin A promoter. In addition, enforced expression of cyclin A releases p120(E4F)-a rrested cells from the G(1) block These data identify the cyclin A gene as a cellular target for p120(E4F) and suggest a mechanism for p120(E4F)-depen dent cell cycle regulation.