Independent cyclic AMP and E1A induction of adenovirus early region 4 expression

A cellular transcription factor, ATF, binds to a repeated element in the adenovirus early region 4 (E4) promoter. ATF also binds to other viral early promoter regions and to the cyclic AMP (cAMP) response elements of cellular genes. In this report, we demonstrate that a single ATF-binding site located immediately upstream of the E4 TATA box, between -62 and -46, mediates induction of E4 transcription by 8-bromoadenosine-3',5-cyclic monophosphate or cholera toxin in the human hepatoma cell line HepG2 and rat pheochromocytoma cell line PC12. Different ATF-binding sites in the E4 control region independently conferred cAMP inducibility on the simian virus 40 early promoter in PC12 cells. Induction of E4 expression by cAMP was also observed in virus-infected HepG2 cells. Other viral early promoter regions that contain ATF-binding sites (E1A and E2A) were also induced by cAMP in infected cells. E4 expression was activated by the E1A 13S mRNA products in HepG2 cells. E1A trans activation appears to be distinct from the cAMP response.