ADENOVIRUS E1A ACTIVATES CYCLIN-A GENE-TRANSCRIPTION IN THE ABSENCE OF GROWTH-FACTORS THROUGH INTERACTION WITH P107

Using the infection of quiescent human fibroblasts with adenovirus typ e 5 and various deletion mutants, we show that E1A can stimulate trans cription of the cyclin A gene in the absence of exogenous growth facto rs. Required for this activity is conserved region 2 (CR2), while both the N-terminal part of E1A and CR1 are dispensable. This indicates th at activation of cyclin A gene expression requires the binding of E1A to p107, while binding to either pRB or p300 is not involved in transc riptional activation. We demonstrate that p107 represses the cyclin A promoter through its cell cycle-regulatory E2F binding site and that 1 2S E1A can activate the cyclin A promoter, essentially by counteractin g its repression by p107. Since CR2 is required for cell transformatio n, transcriptional activation of the cyclin A gene by E1A appears to b e important for its capacity to override control of cellular growth.