Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Oct;85(19):7192–7196. doi: 10.1073/pnas.85.19.7192

Cyclic AMP induction of early adenovirus promoters involves sequences required for E1A trans-activation.

P Sassone-Corsi 1
PMCID: PMC282150  PMID: 2902626

Abstract

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.

Full text

PDF
7192

Images in this article

7193Image
on p.7193
7193Image
on p.7193
7193Image
on p.7193
7194Image
on p.7194
7194Image
on p.7194
7195Image
on p.7195

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berk A. J., Lee F., Harrison T., Williams J., Sharp P. A. Pre-early adenovirus 5 gene product regulates synthesis of early viral messenger RNAs. Cell. 1979 Aug;17(4):935–944. doi: 10.1016/0092-8674(79)90333-7. [DOI] [PubMed] [Google Scholar]
  2. Borrelli E., Hen R., Chambon P. Adenovirus-2 E1A products repress enhancer-induced stimulation of transcription. Nature. 1984 Dec 13;312(5995):608–612. doi: 10.1038/312608a0. [DOI] [PubMed] [Google Scholar]
  3. Borrelli E., Hen R., Wasylyk C., Wasylyk B., Chambon P. The immunoglobulin heavy chain enhancer is stimulated by the adenovirus type 2 E1A products in mouse fibroblasts. Proc Natl Acad Sci U S A. 1986 May;83(9):2846–2849. doi: 10.1073/pnas.83.9.2846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Delegeane A. M., Ferland L. H., Mellon P. L. Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements. Mol Cell Biol. 1987 Nov;7(11):3994–4002. doi: 10.1128/mcb.7.11.3994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
  7. Fisch T. M., Prywes R., Roeder R. G. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore. Mol Cell Biol. 1987 Oct;7(10):3490–3502. doi: 10.1128/mcb.7.10.3490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Garcia J., Wu F., Gaynor R. Upstream regulatory regions required to stabilize binding to the TATA sequence in an adenovirus early promoter. Nucleic Acids Res. 1987 Oct 26;15(20):8367–8385. doi: 10.1093/nar/15.20.8367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hen R., Borrelli E., Chambon P. Repression of the immunoglobulin heavy chain enhancer by the adenovirus-2 E1A products. Science. 1985 Dec 20;230(4732):1391–1394. doi: 10.1126/science.2999984. [DOI] [PubMed] [Google Scholar]
  11. Hen R., Borrelli E., Fromental C., Sassone-Corsi P., Chambon P. A mutated polyoma virus enhancer which is active in undifferentiated embryonal carcinoma cells is not repressed by adenovirus-2 E1A products. Nature. 1986 May 15;321(6067):249–251. doi: 10.1038/321249a0. [DOI] [PubMed] [Google Scholar]
  12. Hurst H. C., Jones N. C. Identification of factors that interact with the E1A-inducible adenovirus E3 promoter. Genes Dev. 1987 Dec;1(10):1132–1146. doi: 10.1101/gad.1.10.1132. [DOI] [PubMed] [Google Scholar]
  13. Imperiale M. J., Hart R. P., Nevins J. R. An enhancer-like element in the adenovirus E2 promoter contains sequences essential for uninduced and E1A-induced transcription. Proc Natl Acad Sci U S A. 1985 Jan;82(2):381–385. doi: 10.1073/pnas.82.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones N., Shenk T. An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3665–3669. doi: 10.1073/pnas.76.8.3665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kao H. T., Nevins J. R. Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Mol Cell Biol. 1983 Nov;3(11):2058–2065. doi: 10.1128/mcb.3.11.2058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lee K. A., Hai T. Y., SivaRaman L., Thimmappaya B., Hurst H. C., Jones N. C., Green M. R. A cellular protein, activating transcription factor, activates transcription of multiple E1A-inducible adenovirus early promoters. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8355–8359. doi: 10.1073/pnas.84.23.8355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leff T., Corden J., Elkaim R., Sassone-Corsi P. Transcriptional analysis of the adenovirus-5 EIII promoter: absence of sequence specificity for stimulation by EIa gene products. Nucleic Acids Res. 1985 Feb 25;13(4):1209–1221. doi: 10.1093/nar/13.4.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leff T., Elkaim R., Goding C. R., Jalinot P., Sassone-Corsi P., Perricaudet M., Kédinger C., Chambon P. Individual products of the adenovirus 12S and 13S EIa mRNAs stimulate viral EIIa and EIII expression at the transcriptional level. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4381–4385. doi: 10.1073/pnas.81.14.4381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lillie J. W., Green M., Green M. R. An adenovirus E1a protein region required for transformation and transcriptional repression. Cell. 1986 Sep 26;46(7):1043–1051. doi: 10.1016/0092-8674(86)90704-x. [DOI] [PubMed] [Google Scholar]
  20. Montminy M. R., Bilezikjian L. M. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature. 1987 Jul 9;328(6126):175–178. doi: 10.1038/328175a0. [DOI] [PubMed] [Google Scholar]
  21. Montminy M. R., Sevarino K. A., Wagner J. A., Mandel G., Goodman R. H. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682–6686. doi: 10.1073/pnas.83.18.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moran E., Mathews M. B. Multiple functional domains in the adenovirus E1A gene. Cell. 1987 Jan 30;48(2):177–178. doi: 10.1016/0092-8674(87)90418-1. [DOI] [PubMed] [Google Scholar]
  23. Reichel R., Kovesdi I., Nevins J. R. Activation of a preexisting cellular factor as a basis for adenovirus E1A-mediated transcription control. Proc Natl Acad Sci U S A. 1988 Jan;85(2):387–390. doi: 10.1073/pnas.85.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sassone-Corsi P., Borrelli E. Promoter trans-activation of protooncogenes c-fos and c-myc, but not c-Ha-ras, by products of adenovirus early region 1A. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6430–6433. doi: 10.1073/pnas.84.18.6430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sassone-Corsi P., Hen R., Borrelli E., Leff T., Chambon P. Far upstream sequences are required for efficient transcription from the adenovirus-2 E1A transcription unit. Nucleic Acids Res. 1983 Dec 20;11(24):8735–8745. doi: 10.1093/nar/11.24.8735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sassone-Corsi P., Wildeman A., Chambon P. A trans-acting factor is responsible for the simian virus 40 enhancer activity in vitro. Nature. 1985 Feb 7;313(6002):458–463. doi: 10.1038/313458a0. [DOI] [PubMed] [Google Scholar]
  27. Simon M. C., Fisch T. M., Benecke B. J., Nevins J. R., Heintz N. Definition of multiple, functionally distinct TATA elements, one of which is a target in the hsp70 promoter for E1A regulation. Cell. 1988 Mar 11;52(5):723–729. doi: 10.1016/0092-8674(88)90410-2. [DOI] [PubMed] [Google Scholar]
  28. SivaRaman L., Thimmappaya B. Two promoter-specific host factors interact with adjacent sequences in an EIA-inducible adenovirus promoter. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6112–6116. doi: 10.1073/pnas.84.17.6112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stein R., Ziff E. B. HeLa cell beta-tubulin gene transcription is stimulated by adenovirus 5 in parallel with viral early genes by an E1a-dependent mechanism. Mol Cell Biol. 1984 Dec;4(12):2792–2801. doi: 10.1128/mcb.4.12.2792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Van Buskirk R., Corcoran T., Wagner J. A. Clonal variants of PC12 pheochromocytoma cells with defects in cAMP-dependent protein kinases induce ornithine decarboxylase in response to nerve growth factor but not to adenosine agonists. Mol Cell Biol. 1985 Aug;5(8):1984–1992. doi: 10.1128/mcb.5.8.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Velcich A., Ziff E. Adenovirus E1a proteins repress transcription from the SV40 early promoter. Cell. 1985 Mar;40(3):705–716. doi: 10.1016/0092-8674(85)90219-3. [DOI] [PubMed] [Google Scholar]
  32. Verma I. M., Sassone-Corsi P. Proto-oncogene fos: complex but versatile regulation. Cell. 1987 Nov 20;51(4):513–514. doi: 10.1016/0092-8674(87)90115-2. [DOI] [PubMed] [Google Scholar]
  33. Weeks D. L., Jones N. C. E1A control of gene expression is mediated by sequences 5' to the transcriptional starts of the early viral genes. Mol Cell Biol. 1983 Jul;3(7):1222–1234. doi: 10.1128/mcb.3.7.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wu L., Rosser D. S., Schmidt M. C., Berk A. A TATA box implicated in E1A transcriptional activation of a simple adenovirus 2 promoter. Nature. 1987 Apr 2;326(6112):512–515. doi: 10.1038/326512a0. [DOI] [PubMed] [Google Scholar]
  35. Zajchowski D. A., Boeuf H., Kédinger C. The adenovirus-2 early EIIa transcription unit possesses two overlapping promoters with different sequence requirements for EIa-dependent stimulation. EMBO J. 1985 May;4(5):1293–1300. doi: 10.1002/j.1460-2075.1985.tb03775.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES