The adenovirus oncoprotein E1a stimulates binding of transcription factor ETF to transcriptionally activate the p53 gene

Expression of the tumor suppressor protein p53 plays an important role in r egulating the cellular response to DNA damage. During adenovirus infection, levels of p53 protein also increase. It has been shown that this increase is due not only to increased stability of the p53 protein but to the transc riptional activation of the p53 gene during infection. We demonstrate here that the E1a proteins of adenovirus are responsible for activating the mous e p53 gene and that both major E1a proteins, 243R and 289R, are required fo r complete activation. E1a brings about the binding of two cellular transcr iption factors to the mouse p53 promoter. One of these, ETF, binds to three upstream sites in the p53 promoter and one downstream site, whereas E2F bi nds to one upstream site in the presence of E1a. Our studies indicate that E2F binding is not essential for activation of the p53 promoter but that ET F is. Our data indicate the ETF site located downstream of the start site o f transcription is the key site in conferring E1a responsiveness on the p53 promoter.