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. 1987 Nov;6(11):3399–3405. doi: 10.1002/j.1460-2075.1987.tb02663.x

Activation of adenovirus 5 E1A transcription by region E1B in transformed primary rat cells.

A G Jochemsen 1, L T Peltenburg 1, M F te Pas 1, C M de Wit 1, J L Bos 1, A J van der Eb 1
PMCID: PMC553797  PMID: 2962857

Abstract

The human adenovirus 5 E1A region can immortalize primary cultures of baby rat kidney cells, but requires the presence of the E1B region for complete oncogenic transformation. One of the effects of the E1B region in the transformation process is the activation of E1A expression. We have investigated the mechanism of this stimulation of E1A expression using nuclear run-on assays with nuclei from Ad5 E1A- and Ad5 E1-transformed cells. It was found that E1B enhances E1A at the level of transcription-initiation. This activation is mainly observed when the E1A and E1B regions are integrated simultaneously into the cellular genome and only minimally when these genes are integrated separately, strongly suggesting that a close physical linkage of these regions is essential for the observed effect.

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Selected References

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

  1. Berk A. J. Adenovirus promoters and E1A transactivation. Annu Rev Genet. 1986;20:45–79. doi: 10.1146/annurev.ge.20.120186.000401. [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., Van der Eb A. J. Adenovirus: transformation and oncogenicity. Biochim Biophys Acta. 1984 Dec 14;783(3):187–204. doi: 10.1016/0167-4781(84)90029-0. [DOI] [PubMed] [Google Scholar]
  5. Bernards R., de Leeuw M. G., Houweling A., van der Eb A. J. Role of the adenovirus early region 1B tumor antigens in transformation and lytic infection. Virology. 1986 Apr 15;150(1):126–139. doi: 10.1016/0042-6822(86)90272-2. [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. 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]
  9. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  11. Gallimore P. H., Byrd P. J., Whittaker J. L., Grand R. J. Properties of rat cells transformed by DNA plasmids containing adenovirus type 12 E1 DNA or specific fragments of the E1 region: comparison of transforming frequencies. Cancer Res. 1985 Jun;45(6):2670–2680. [PubMed] [Google Scholar]
  12. Harlow E., Franza B. R., Jr, Schley C. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol. 1985 Sep;55(3):533–546. doi: 10.1128/jvi.55.3.533-546.1985. [DOI] [PMC free article] [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. Jochemsen A. G., Bernards R., van Kranen H. J., Houweling A., Bos J. L., van der Eb A. J. Different activities of the adenovirus types 5 and 12 E1A regions in transformation with the EJ Ha-ras oncogene. J Virol. 1986 Sep;59(3):684–691. doi: 10.1128/jvi.59.3.684-691.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jochemsen A. G., Bos J. L., van der Eb A. J. The first exon of region E1a genes of adenoviruses 5 and 12 encodes a separate functional protein domain. EMBO J. 1984 Dec 1;3(12):2923–2927. doi: 10.1002/j.1460-2075.1984.tb02233.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jochemsen A. G., de Wit C. M., Bos J. L., van der Eb A. J. Transforming properties of a 15-kDa truncated Ad12 E1A gene product. Virology. 1986 Jul 30;152(2):375–383. doi: 10.1016/0042-6822(86)90140-6. [DOI] [PubMed] [Google Scholar]
  17. Jochemsen H., Daniëls G. S., Hertoghs J. J., Schrier P. I., van den Elsen P. J., van der EB A. J. Identification of adenovirus-type 12 gene products involved in transformation and oncogenesis. Virology. 1982 Oct 15;122(1):15–28. doi: 10.1016/0042-6822(82)90373-7. [DOI] [PubMed] [Google Scholar]
  18. Katze M. G., Persson H., Philipson L. A novel mRNA and a low molecular weight polypeptide encoded in the transforming region of adenovirus DNA. EMBO J. 1982;1(7):783–789. doi: 10.1002/j.1460-2075.1982.tb01248.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lucher L. A., Brackmann K. H., Symington J. S., Green M. Antibody directed to a synthetic peptide encoding the NH2-terminal 16 amino acids of the adenovirus type 2 E1B-53K tumor antigen recognizes the E1B-20K tumor antigen. Virology. 1984 Jan 15;132(1):217–221. doi: 10.1016/0042-6822(84)90106-5. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Roberts B. E., Miller J. S., Kimelman D., Cepko C. L., Lemischka I. R., Mulligan R. C. Individual adenovirus type 5 early region 1A gene products elicit distinct alterations of cellular morphology and gene expression. J Virol. 1985 Nov;56(2):404–413. doi: 10.1128/jvi.56.2.404-413.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Senear A. W., Lewis J. B. Morphological transformation of established rodent cell lines by high-level expression of the adenovirus type 2 E1a gene. Mol Cell Biol. 1986 Apr;6(4):1253–1260. doi: 10.1128/mcb.6.4.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Vaessen R. T., Houweling A., van der Eb A. J. Post-transcriptional control of class I MHC mRNA expression in adenovirus 12-transformed cells. Science. 1987 Mar 20;235(4795):1486–1488. doi: 10.1126/science.3823900. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Virtanen A., Pettersson U., Le Moullec J. M., Tiollais P., Perricaudet M. Different mRNAs from the transforming region of highly oncogenic and non-oncogenic human adenoviruses. Nature. 1982 Feb 25;295(5851):705–707. doi: 10.1038/295705a0. [DOI] [PubMed] [Google Scholar]
  26. Virtanen A., Pettersson U. Organization of early region 1B of human adenovirus type 2: identification of four differentially spliced mRNAs. J Virol. 1985 May;54(2):383–391. doi: 10.1128/jvi.54.2.383-391.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilson M. C., Darnell J. E., Jr Control of messenger RNA concentration by differential cytoplasmic half-life. Adenovirus messenger RNAs from transcription units 1A and 1B. J Mol Biol. 1981 May 25;148(3):231–251. doi: 10.1016/0022-2836(81)90537-4. [DOI] [PubMed] [Google Scholar]
  28. Wilson M. C., Fraser N. W., Darnell J. E., Jr Mapping of RNA initiation sites by high doses of uv irradiation: evidence for three independent promoters within the left 11% of the Ad-2 genome. Virology. 1979 Apr 15;94(1):175–184. doi: 10.1016/0042-6822(79)90447-1. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. van den Elsen P., de Pater S., Houweling A., van der Veer J., van der Eb A. The relationship between region E1a and E1b of human adenoviruses in cell transformation. Gene. 1982 May;18(2):175–185. doi: 10.1016/0378-1119(82)90115-9. [DOI] [PubMed] [Google Scholar]
  31. 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]

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