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

Abstract

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 $49 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.

Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP.

“…Engel and T. Shenk, unpubL). Furthermore, El A and cAMP activate some of these genes synergistically, indicating that the cAMP-mediated and El A-me diated responses are somehow linked or interactive (Engel et al 1988). To date, no direct effect of ElA on ATF has been reported; the DNA binding activity of ATF is not increased during infection of HeLa cells with adenovirus SivaRaman and Thimmappaya 1987).…”

“…We demonstrated previously that cAMP and ElA pro teins act in synergy to induce transcription of ElA-in ducible adenovirus genes (Engel et al 1988). This obser vation was pursued by searching for transcription factors present in S49 cells that were altered upon infection and cAMP treatment.…”

“…Uninfected and adenovirus-infected S49 cells were treated with BtjcAMP for various lengths of time. Infected cells were harvested 24 hr after infection, before the onset of DNA replication, which occurred at 30-36 hr (Engel et al 1988). Nuclear extracts were prepared, and AP-1 activity was evaluated by band-shift assay (Fried and Crothers 1981) using a ^^P-labeled, double-stranded 35-bp oligonucleotide con taining the AP-1 binding site from the collagenase gene promoter (Angel et al 1987).…”

“…In fact, cAMP can induce the transcription of the adenovirus E2, E3, and E4 genes in transient transfection experiments (Sassone-Corsi 1988;Leza and Hearing 1989). In adenovirusinfected mouse S49 cells, cAMP activates the transcrip tion of the ElA, ElB, E2, E3, and E4 genes (Engel et al 1988;D.A. Engel and T. Shenk, unpubL).…”

“…Because cAMP and ElA can synergize to activate the transcription of ElA-inducible genes in mouse S49 cells (Engel et al 1988), we endeavored to identify transcrip tion factors that mediate this effect. Employing DNA binding assays, we observed that the transcription factor AP-1 is activated to a modest extent by cAMP and to significantly higher levels by cAMP in adenovirus-infected cells.…”