Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1984 Dec 1;3(12):2923–2927. doi: 10.1002/j.1460-2075.1984.tb02233.x

The first exon of region E1a genes of adenoviruses 5 and 12 encodes a separate functional protein domain.

A G Jochemsen, J L Bos, A J van der Eb
PMCID: PMC557790  PMID: 6098455

Abstract

The transforming E1 regions of human adenoviruses Ad5 and Ad12 differ from each other in the frequency by which they can transform primary baby rat kidney cells, and in their ability to modulate expression of class I major histocompatibility (MHC) genes. We have investigated whether these two properties, which are determined by region E1a, can be assigned to one of the two protein segments encoded by the E1a exons. To that end, we have constructed chimaeric E1a regions, in which the 5' E1a exon of Ad5 was linked to the 3' E1a exon of Ad12, and vice versa. It was found that, although there is only a limited degree of homology between Ad5 and Ad12 E1a (approximately 40% at the protein level), the hybrid E1a products are functional in transformation. Furthermore, both the frequency of transformation and the modulation of class I MHC gene expression appeared to be determined by the first E1a exon. These results indicate that the first E1a exon encodes a separate functional domain in the E1a proteins.

Full text

PDF
2923

Images in this article

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. Bernards R., Houweling A., Schrier P. I., Bos J. L., Van der Eb A. J. Characterization of cells transformed by Ad5/Ad12 hybrid early region I plasmids. Virology. 1982 Jul 30;120(2):422–432. doi: 10.1016/0042-6822(82)90042-3. [DOI] [PubMed] [Google Scholar]
  3. Bernards R., Schrier P. I., Bos J. L., Van der Eb A. J. Role of adenovirus types 5 and 12 early region 1b tumor antigens in oncogenic transformation. Virology. 1983 May;127(1):45–53. doi: 10.1016/0042-6822(83)90369-0. [DOI] [PubMed] [Google Scholar]
  4. Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
  5. Bos J. L., Jochemsen A. G., Bernards R., Schrier P. I., van Ormondt H., van der Eb A. J. Deletion mutants of region E1a of AD12 E1 plasmids: effect on oncogenic transformation. Virology. 1983 Sep;129(2):393–400. doi: 10.1016/0042-6822(83)90178-2. [DOI] [PubMed] [Google Scholar]
  6. Bos J. L., Polder L. J., Bernards R., Schrier P. I., van den Elsen P. J., van der Eb A. J., van Ormondt H. The 2.2 kb E1b mRNA of human Ad12 and Ad5 codes for two tumor antigens starting at different AUG triplets. Cell. 1981 Nov;27(1 Pt 2):121–131. doi: 10.1016/0092-8674(81)90366-4. [DOI] [PubMed] [Google Scholar]
  7. Bos J. L., ten Wolde-Kraamwinkel H. C. The E1b promoter of Ad12 in mouse L tk- cells is activated by adenovirus region E1a. EMBO J. 1983;2(1):73–76. doi: 10.1002/j.1460-2075.1983.tb01383.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Esche H., Mathews M. B., Lewis J. B. Proteins and messenger RNAs of the transforming region of wild-type and mutant adenoviruses. J Mol Biol. 1980 Sep 25;142(3):399–417. doi: 10.1016/0022-2836(80)90279-x. [DOI] [PubMed] [Google Scholar]
  9. Esche H., Siegmann B. Expression of early viral gene products in adenovirus type 12-infected and -transformed cells. J Gen Virol. 1982 May;60(Pt 1):99–113. doi: 10.1099/0022-1317-60-1-99. [DOI] [PubMed] [Google Scholar]
  10. Graham F. L., Harrison T., Williams J. Defective transforming capacity of adenovirus type 5 host-range mutants. Virology. 1978 May 1;86(1):10–21. doi: 10.1016/0042-6822(78)90003-x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Ho Y. S., Galos R., Williams J. Isolation of type 5 adenovirus mutants with a cold-sensitive host range phenotype: genetic evidence of an adenovirus transformation maintenance function. Virology. 1982 Oct 15;122(1):109–124. doi: 10.1016/0042-6822(82)90381-6. [DOI] [PubMed] [Google Scholar]
  13. Houweling A., van den Elsen P. J., van der Eb A. J. Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA. Virology. 1980 Sep;105(2):537–550. doi: 10.1016/0042-6822(80)90054-9. [DOI] [PubMed] [Google Scholar]
  14. Luciw P. A., Bishop J. M., Varmus H. E., Capecchi M. R. Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. Cell. 1983 Jul;33(3):705–716. doi: 10.1016/0092-8674(83)90013-2. [DOI] [PubMed] [Google Scholar]
  15. Montell C., Courtois G., Eng C., Berk A. Complete transformation by adenovirus 2 requires both E1A proteins. Cell. 1984 Apr;36(4):951–961. doi: 10.1016/0092-8674(84)90045-x. [DOI] [PubMed] [Google Scholar]
  16. Montell C., Fisher E. F., Caruthers M. H., Berk A. J. Resolving the functions of overlapping viral genes by site-specific mutagenesis at a mRNA splice site. Nature. 1982 Feb 4;295(5848):380–384. doi: 10.1038/295380a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  20. Schrier P. I., Van Den Elsen P. J., Hertoghs J. J., Van Der Eb A. J. Characterization of tumor antigens in cells transformed by fragments of adenovirus type 5 DNA. Virology. 1979 Dec;99(2):372–385. doi: 10.1016/0042-6822(79)90016-3. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Winberg G., Shenk T. Dissection of overlapping functions within the adenovirus type 5 E1A gene. EMBO J. 1984 Aug;3(8):1907–1912. doi: 10.1002/j.1460-2075.1984.tb02066.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. van der Eb A. J., Graham F. L. Assay of transforming activity of tumor virus DNA. Methods Enzymol. 1980;65(1):826–839. doi: 10.1016/s0076-6879(80)65077-0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES