c-myc products trans-activate the adenovirus E4 promoter in EC stem cells by using the same target sequence as E1A products

Abstract

Using a short-term transfection assay, we show that the E4 early adenovirus promoter is expressed to a certain extent in undifferentiated F9 and PCC4 cells, which are known to possess cellular E1A-like activity. We have also observed that c-myc products trans-activate the E4 promoter in EC stem cells and HeLa cells. Using 5' deletion mutants of the E4 promoter, we show that the same target sequence is used by c-myc and E1A. This sequence is located between positions -179 and -158 upstream of the cap site and is known to contain an activating transcription factor (ATF)-binding site. Moreover, the basal of level of activity of the deletion mutants. is related to the number of ATF binding sites. We therefore suggest that c-myc is a functional cellular homolog of the viral E1A gene and that it might correspond to one of the cellular E1A-like activities previously described for EC stem cells. We have also observed that only a c-myc plasmid coding for both p67 and 64 proteins, in contrast to one coding for p64 only, is able to trans-activate the E4 and E2A adenovirus promoter, suggesting that the p67 protein plays an essential part in activation.