Cyclic AMP induction of early adenovirus promoters involves sequences required for E1A trans-activation.
Early in adenovirus infection, the E1A (early region 1A) oncogene products trans-activate the other early viral transcription units, as well as some cellular promoters. The mechanism by which E1A elicits its activity is still unknown. In this report, I show that the adenovirus E2a and E3 promoters are cAMP inducible in rat pheochromocytoma PC12 cells and that this activation requires the presence of the cAMP-dependent protein kinase II. Using deletion mutants of the E2a promoter, it was found that the sequence TACGTCAT located between positions -70 and -77 is involved in both the cAMP response and the E1A trans-activation. Also, in the mutant PC12 cell line A126-2B, which lacks the cAMP-dependent protein kinase II, E1A is still able to activate E2a and E3 promoters. This suggests that E1A products may circumvent the lack of the kinase by activating an alternative signal transduction pathway, which could mimic the effect of agonists of adenylate cyclase. I propose that E1A is capable of modifying by phosphorylation, either directly or indirectly, the transcription factor that binds the ACGTCA motif. Such a factor, termed ATF (adenovirus transcription factor), has already been characterized and appears to have strong similarities to the transcriptional factor CREB (cAMP responsive element binding protein), which binds homologous sequences in cAMP responsive genes, such as somatostatin and c-fos.
D000256:Adenoviridae / Q000235:genetics*; D017456:Adenovirus Early Proteins; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D005801:Genes, Homeobox; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D017456:Adenovirus Early Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D000242:Cyclic AMP; D011494:Protein Kinases