Cyclin A Is a Mediator of p120(E4F)-Dependent Cell Cycle Arrest in G(1)

E4F is a ubiquitously expressed GLI-Krüppel-related transcription factor which has been identified for its capacity to regulate transcription of the adenovirus E4 gene in response to E1A. However, cellular genes regulated by E4F are still unknown. Some of these genes are likely to be involved in cell cycle progression since ectopic p120(E4F) expression induces cell cycle arrest 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) block in p21(−/−) cells, suggesting that other proteins are essential for the p120(E4F)-dependent block in G(1). We show here that cyclin A promoter activity can be repressed by p120(E4F) and that this repression correlates with p120(E4F) binding to the cyclic AMP-responsive element site of the cyclin A promoter. In addition, enforced expression of cyclin A releases p120(E4F)-arrested 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)-dependent cell cycle regulation.