Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1986 Dec 9;14(23):9445–9456. doi: 10.1093/nar/14.23.9445

Adenovirus-2 E1a and E1b gene products regulate enhancer mediated transcription.

V Natarajan
PMCID: PMC311969  PMID: 2948155

Abstract

We have shown that adenovirus-2 early region 1 gene products in trans and the SV40 enhancer in cis have an additive effect in stimulating transcription from adenovirus IVa2 and major late promoters (Natarajan, V. and Salzman, N. P., Nucleic Acids Research 13, 4067, 1985). In the present study, we show that both the E1a and E1b gene products are necessary for this stimulatory effect on enhancer mediated transcription. In the absence of E1b region, the transcription is strongly suppressed by E1a. Transcription from E1a promoter is also stimulated 4-5 fold in the presence of E1b region. The data suggest that 21K protein coded by the E1b region modulates transcription from the E1a promoter and the action of E1a gene products on transcription from other promoters.

Full text

PDF
9445

Images in this article

9448Image
on p.9448
9450Image
on p.9450
9451Image
on p.9451
9453Image
on p.9453

Selected References

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

  1. Babiss L. E., Ginsberg H. S., Darnell J. E., Jr Adenovirus E1B proteins are required for accumulation of late viral mRNA and for effects on cellular mRNA translation and transport. Mol Cell Biol. 1985 Oct;5(10):2552–2558. doi: 10.1128/mcb.5.10.2552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker C. C., Ziff E. B. Promoters and heterogeneous 5' termini of the messenger RNAs of adenovirus serotype 2. J Mol Biol. 1981 Jun 25;149(2):189–221. doi: 10.1016/0022-2836(81)90298-9. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bishop J. M. Viral oncogenes. Cell. 1985 Aug;42(1):23–38. doi: 10.1016/s0092-8674(85)80098-2. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Branton P. E., Bayley S. T., Graham F. L. Transformation by human adenoviruses. Biochim Biophys Acta. 1985;780(1):67–94. doi: 10.1016/0304-419x(84)90007-6. [DOI] [PubMed] [Google Scholar]
  8. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  9. Chinnadurai G. Adenovirus 2 Ip+ locus codes for a 19 kd tumor antigen that plays an essential role in cell transformation. Cell. 1983 Jul;33(3):759–766. doi: 10.1016/0092-8674(83)90018-1. [DOI] [PubMed] [Google Scholar]
  10. D'Halluin J. C., Delsert C., Milleville M., Boulanger P. An adenovirus cytocidal function related to the control of a cellular pH 4 endonuclease activity. J Gen Virol. 1985 Sep;66(Pt 9):1873–1887. doi: 10.1099/0022-1317-66-9-1873. [DOI] [PubMed] [Google Scholar]
  11. Darnell J. E., Jr Variety in the level of gene control in eukaryotic cells. Nature. 1982 Jun 3;297(5865):365–371. doi: 10.1038/297365a0. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Gaynor R. B., Hillman D., Berk A. J. Adenovirus early region 1A protein activates transcription of a nonviral gene introduced into mammalian cells by infection or transfection. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1193–1197. doi: 10.1073/pnas.81.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gingeras T. R., Sciaky D., Gelinas R. E., Bing-Dong J., Yen C. E., Kelly M. M., Bullock P. A., Parsons B. L., O'Neill K. E., Roberts R. J. Nucleotide sequences from the adenovirus-2 genome. J Biol Chem. 1982 Nov 25;257(22):13475–13491. [PubMed] [Google Scholar]
  15. 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]
  16. Green M. R., Treisman R., Maniatis T. Transcriptional activation of cloned human beta-globin genes by viral immediate-early gene products. Cell. 1983 Nov;35(1):137–148. doi: 10.1016/0092-8674(83)90216-7. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Imperiale M. J., Feldman L. T., Nevins J. R. Activation of gene expression by adenovirus and herpesvirus regulatory genes acting in trans and by a cis-acting adenovirus enhancer element. Cell. 1983 Nov;35(1):127–136. doi: 10.1016/0092-8674(83)90215-5. [DOI] [PubMed] [Google Scholar]
  20. Imperiale M. J., Kao H. T., Feldman L. T., Nevins J. R., Strickland S. Common control of the heat shock gene and early adenovirus genes: evidence for a cellular E1A-like activity. Mol Cell Biol. 1984 May;4(5):867–874. doi: 10.1128/mcb.4.5.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Khoury G., Gruss P. Enhancer elements. Cell. 1983 Jun;33(2):313–314. doi: 10.1016/0092-8674(83)90410-5. [DOI] [PubMed] [Google Scholar]
  23. Kingston R. E., Baldwin A. S., Sharp P. A. Transcription control by oncogenes. Cell. 1985 May;41(1):3–5. doi: 10.1016/0092-8674(85)90049-2. [DOI] [PubMed] [Google Scholar]
  24. Kovesdi I., Reichel R., Nevins J. R. E1A transcription induction: enhanced binding of a factor to upstream promoter sequences. Science. 1986 Feb 14;231(4739):719–722. doi: 10.1126/science.2935935. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Manley J. L. Analysis of the expression of genes encoding animal mRNA by in vitro techniques. Prog Nucleic Acid Res Mol Biol. 1983;30:195–244. doi: 10.1016/s0079-6603(08)60687-x. [DOI] [PubMed] [Google Scholar]
  27. Murthy S. C., Bhat G. P., Thimmappaya B. Adenovirus EIIA early promoter: transcriptional control elements and induction by the viral pre-early EIA gene, which appears to be sequence independent. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2230–2234. doi: 10.1073/pnas.82.8.2230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Natarajan V., Madden M. J., Salzman N. P. Preferential stimulation of transcription from simian virus 40 late and adeno IVa2 promoters in a HeLa cell extract. J Biol Chem. 1983 Dec 10;258(23):14652–14655. [PubMed] [Google Scholar]
  29. Natarajan V., Salzman N. P. Cis and trans activation of adenovirus IVa2 gene transcription. Nucleic Acids Res. 1985 Jun 11;13(11):4067–4083. doi: 10.1093/nar/13.11.4067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nevins J. R. Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell. 1982 Jul;29(3):913–919. doi: 10.1016/0092-8674(82)90453-6. [DOI] [PubMed] [Google Scholar]
  31. Nevins J. R. Mechanism of activation of early viral transcription by the adenovirus E1A gene product. Cell. 1981 Oct;26(2 Pt 2):213–220. doi: 10.1016/0092-8674(81)90304-4. [DOI] [PubMed] [Google Scholar]
  32. Parker B. A., Stark G. R. Regulation of simian virus 40 transcription: sensitive analysis of the RNA species present early in infections by virus or viral DNA. J Virol. 1979 Aug;31(2):360–369. doi: 10.1128/jvi.31.2.360-369.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pilder S., Logan J., Shenk T. Deletion of the gene encoding the adenovirus 5 early region 1b 21,000-molecular-weight polypeptide leads to degradation of viral and host cell DNA. J Virol. 1984 Nov;52(2):664–671. doi: 10.1128/jvi.52.2.664-671.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rossini M. The role of adenovirus early region 1A in the regulation of early regions 2A and 1B expression. Virology. 1983 Nov;131(1):49–58. doi: 10.1016/0042-6822(83)90532-9. [DOI] [PubMed] [Google Scholar]
  35. Smith D. H., Kegler D. M., Ziff E. B. Vector expression of adenovirus type 5 E1a proteins: evidence for E1a autoregulation. Mol Cell Biol. 1985 Oct;5(10):2684–2696. doi: 10.1128/mcb.5.10.2684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Solnick D., Anderson M. A. Transformation-deficient adenovirus mutant defective in expression of region 1A but not region 1B. J Virol. 1982 Apr;42(1):106–113. doi: 10.1128/jvi.42.1.106-113.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Subramanian T., Kuppuswamy M., Gysbers J., Mak S., Chinnadurai G. 19-kDa tumor antigen coded by early region E1b of adenovirus 2 is required for efficient synthesis and for protection of viral DNA. J Biol Chem. 1984 Oct 10;259(19):11777–11783. [PubMed] [Google Scholar]
  38. Subramanian T., Kuppuswamy M., Mak S., Chinnadurai G. Adenovirus cyt+ locus, which controls cell transformation and tumorigenicity, is an allele of lp+ locus, which codes for a 19-kilodalton tumor antigen. J Virol. 1984 Nov;52(2):336–343. doi: 10.1128/jvi.52.2.336-343.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Svensson C., Akusjärvi G. Adenovirus 2 early region 1A stimulates expression of both viral and cellular genes. EMBO J. 1984 Apr;3(4):789–794. doi: 10.1002/j.1460-2075.1984.tb01886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Takemori N., Cladaras C., Bhat B., Conley A. J., Wold W. S. cyt gene of adenoviruses 2 and 5 is an oncogene for transforming function in early region E1B and encodes the E1B 19,000-molecular-weight polypeptide. J Virol. 1984 Dec;52(3):793–805. doi: 10.1128/jvi.52.3.793-805.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Van den Elsen P., Houweling A., Van der Eb A. Expression of region E1b of human adenoviruses in the absence of region E1a is not sufficient for complete transformation. Virology. 1983 Jul 30;128(2):377–390. doi: 10.1016/0042-6822(83)90264-7. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. White E., Grodzicker T., Stillman B. W. Mutations in the gene encoding the adenovirus early region 1B 19,000-molecular-weight tumor antigen cause the degradation of chromosomal DNA. J Virol. 1984 Nov;52(2):410–419. doi: 10.1128/jvi.52.2.410-419.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
  45. Yee S. P., Branton P. E. Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. Virology. 1985 Nov;147(1):142–153. doi: 10.1016/0042-6822(85)90234-x. [DOI] [PubMed] [Google Scholar]
  46. van den Elsen P. J., Houweling A., van der Eb A. J. Morphological transformation of human adenoviruses is determined to a large extent by gene products of region E1a. Virology. 1983 Nov;131(1):242–246. doi: 10.1016/0042-6822(83)90549-4. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES