cAMP acts in synergy with E1A protein to activate transcription of the adenovirus early genes E4 and E1A.

The transcriptional control regions of several E1A-inducible adenovirus early genes contain sequences similar to the cAMP response element of several cellular cAMP-inducible genes. The cAMP-responsive cell line S49 was infected with wild-type adenovirus and found to contain elevated levels of mRNAs encoded by all early genes tested (E4, E1A, and E1B), following treatment with dibutyryl cAMP. This effect was at the level of transcriptional activation. The effect of cAMP on E4 and E1A transcription was greater in cells infected with wild-type virus than in cells infected with virus that lacked functional E1A proteins. cAMP in combination with E1A generated a greater induction than the product of the increases achieved by each inducer alone. Therefore, cAMP acted in synergy with E1A to induce maximally transcription of the E4 and E1A genes. These data suggest that E1A or E1A-stimulated events can interact functionally with targets of cAMP signaling in the cell to induce transcription of the adenovirus early genes.