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. 1991 Feb 11;19(3):649–655. doi: 10.1093/nar/19.3.649

E1A dependent up-regulation of c-jun/AP-1 activity.

I Kitabayashi 1, R Chiu 1, G Gachelin 1, K Yokoyama 1
PMCID: PMC333661  PMID: 1826351

Abstract

E1A, the early region 1A transcription unit of human adenovirus, exhibits multiple functions that regulate the expression of some cellular genes and promote cell growth and division. We found that E1A stimulated c-jun gene expression at least fifty-fold in rat 3Y1 cells in a serum-independent manner, concomitantly with E1A down-regulation of jun B expression. The E1A-dependent induction of c-jun transcription resulted in increase amount of cJun/AP1. This induction was mediated by the enhancement of the binding activity of the transcription factor cJun/AP1 to an AP1 binding site in the c-jun promoter. Additionally, this induction can be repressed by introducing junB into the cells. Taken collectively, these results suggest that the differential expression of two closely related proteins greatly expands their cellular regulation. Induction of c-jun expression by E1A as well as c-jun autoregulation may amplify the action of E1A during adenovirus infection. Therefore, some of the biological effects of E1A may include mediating the constitutive activation of c-jun, which is important in transcriptional regulation and oncogenic transformation.

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Selected References

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

  1. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Hattori K., Smeal T., Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875–885. doi: 10.1016/0092-8674(88)90143-2. [DOI] [PubMed] [Google Scholar]
  3. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  7. Brenner D. A., O'Hara M., Angel P., Chojkier M., Karin M. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature. 1989 Feb 16;337(6208):661–663. doi: 10.1038/337661a0. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Chiu R., Angel P., Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell. 1989 Dec 22;59(6):979–986. doi: 10.1016/0092-8674(89)90754-x. [DOI] [PubMed] [Google Scholar]
  10. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  11. Chiu R., Imagawa M., Imbra R. J., Bockoven J. R., Karin M. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Nature. 1987 Oct 15;329(6140):648–651. doi: 10.1038/329648a0. [DOI] [PubMed] [Google Scholar]
  12. Ferguson B., Krippl B., Andrisani O., Jones N., Westphal H., Rosenberg M. E1A 13S and 12S mRNA products made in Escherichia coli both function as nucleus-localized transcription activators but do not directly bind DNA. Mol Cell Biol. 1985 Oct;5(10):2653–2661. doi: 10.1128/mcb.5.10.2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Flint J., Shenk T. Adenovirus E1A protein paradigm viral transactivator. Annu Rev Genet. 1989;23:141–161. doi: 10.1146/annurev.ge.23.120189.001041. [DOI] [PubMed] [Google Scholar]
  14. Graham F. L., van der Eb A. J., Heijneker H. L. Size and location of the transforming region in human adenovirus type 5 DNA. Nature. 1974 Oct 25;251(5477):687–691. doi: 10.1038/251687a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hattori K., Angel P., Le Beau M. M., Karin M. Structure and chromosomal localization of the functional intronless human JUN protooncogene. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9148–9152. doi: 10.1073/pnas.85.23.9148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hirai S. I., Ryseck R. P., Mechta F., Bravo R., Yaniv M. Characterization of junD: a new member of the jun proto-oncogene family. EMBO J. 1989 May;8(5):1433–1439. doi: 10.1002/j.1460-2075.1989.tb03525.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hoeffler W. K., Kovelman R., Roeder R. G. Activation of transcription factor IIIC by the adenovirus E1A protein. Cell. 1988 Jun 17;53(6):907–920. doi: 10.1016/s0092-8674(88)90409-6. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Katoh S., Ozawa K., Kondoh S., Soeda E., Israel A., Shiroki K., Fujinaga K., Itakura K., Gachelin G., Yokoyama K. Identification of sequences responsible for positive and negative regulation by E1A in the promoter of H-2Kbm1 class I MHC gene. EMBO J. 1990 Jan;9(1):127–135. doi: 10.1002/j.1460-2075.1990.tb08088.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kimura G., Itagaki A., Summers J. Rat cell line 3y1 and its virogenic polyoma- and sv40- transformed derivatives. Int J Cancer. 1975 Apr 15;15(4):694–706. doi: 10.1002/ijc.2910150419. [DOI] [PubMed] [Google Scholar]
  22. Kitabayashi I., Saka F., Gachelin G., Yokoyama K. Nucleotide sequence of rat c-jun protooncogene. Nucleic Acids Res. 1990 Jun 11;18(11):3400–3400. doi: 10.1093/nar/18.11.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lamph W. W., Wamsley P., Sassone-Corsi P., Verma I. M. Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature. 1988 Aug 18;334(6183):629–631. doi: 10.1038/334629a0. [DOI] [PubMed] [Google Scholar]
  24. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Liu F., Green M. R. A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein. Cell. 1990 Jun 29;61(7):1217–1224. doi: 10.1016/0092-8674(90)90686-9. [DOI] [PubMed] [Google Scholar]
  27. Macgregor P. F., Abate C., Curran T. Direct cloning of leucine zipper proteins: Jun binds cooperatively to the CRE with CRE-BP1. Oncogene. 1990 Apr;5(4):451–458. [PubMed] [Google Scholar]
  28. Maekawa T., Sakura H., Kanei-Ishii C., Sudo T., Yoshimura T., Fujisawa J., Yoshida M., Ishii S. Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain. EMBO J. 1989 Jul;8(7):2023–2028. doi: 10.1002/j.1460-2075.1989.tb03610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Müller U., Roberts M. P., Engel D. A., Doerfler W., Shenk T. Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP. Genes Dev. 1989 Dec;3(12A):1991–2002. doi: 10.1101/gad.3.12a.1991. [DOI] [PubMed] [Google Scholar]
  31. Nakabeppu Y., Ryder K., Nathans D. DNA binding activities of three murine Jun proteins: stimulation by Fos. Cell. 1988 Dec 2;55(5):907–915. doi: 10.1016/0092-8674(88)90146-8. [DOI] [PubMed] [Google Scholar]
  32. Oshima R. G., Abrams L., Kulesh D. Activation of an intron enhancer within the keratin 18 gene by expression of c-fos and c-jun in undifferentiated F9 embryonal carcinoma cells. Genes Dev. 1990 May;4(5):835–848. doi: 10.1101/gad.4.5.835. [DOI] [PubMed] [Google Scholar]
  33. Pardee A. B. G1 events and regulation of cell proliferation. Science. 1989 Nov 3;246(4930):603–608. doi: 10.1126/science.2683075. [DOI] [PubMed] [Google Scholar]
  34. Rauscher F. J., 3rd, Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohmann D., Tjian R., Franza B. R., Jr Fos-associated protein p39 is the product of the jun proto-oncogene. Science. 1988 May 20;240(4855):1010–1016. doi: 10.1126/science.3130660. [DOI] [PubMed] [Google Scholar]
  35. Raychaudhuri P., Bagchi S., Nevins J. R. DNA-binding activity of the adenovirus-induced E4F transcription factor is regulated by phosphorylation. Genes Dev. 1989 May;3(5):620–627. doi: 10.1101/gad.3.5.620. [DOI] [PubMed] [Google Scholar]
  36. Rickles R. J., Darrow A. L., Strickland S. Differentiation-responsive elements in the 5' region of the mouse tissue plasminogen activator gene confer two-stage regulation by retinoic acid and cyclic AMP in teratocarcinoma cells. Mol Cell Biol. 1989 Apr;9(4):1691–1704. doi: 10.1128/mcb.9.4.1691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rochette-Egly C., Fromental C., Chambon P. General repression of enhanson activity by the adenovirus-2 E1A proteins. Genes Dev. 1990 Jan;4(1):137–150. doi: 10.1101/gad.4.1.137. [DOI] [PubMed] [Google Scholar]
  38. Ryder K., Lanahan A., Perez-Albuerne E., Nathans D. jun-D: a third member of the jun gene family. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1500–1503. doi: 10.1073/pnas.86.5.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ryder K., Lau L. F., Nathans D. A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1487–1491. doi: 10.1073/pnas.85.5.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Schönthal A., Herrlich P., Rahmsdorf H. J., Ponta H. Requirement for fos gene expression in the transcriptional activation of collagenase by other oncogenes and phorbol esters. Cell. 1988 Jul 29;54(3):325–334. doi: 10.1016/0092-8674(88)90195-x. [DOI] [PubMed] [Google Scholar]
  43. Schütte J., Minna J. D., Birrer M. J. Deregulated expression of human c-jun transforms primary rat embryo cells in cooperation with an activated c-Ha-ras gene and transforms rat-1a cells as a single gene. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2257–2261. doi: 10.1073/pnas.86.7.2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schütte J., Viallet J., Nau M., Segal S., Fedorko J., Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell. 1989 Dec 22;59(6):987–997. doi: 10.1016/0092-8674(89)90755-1. [DOI] [PubMed] [Google Scholar]
  45. Shiroki K., Hashimoto S., Saito I., Fukui Y., Fukui Y., Kato H., Shimojo H. Expression of the E4 gene is required for establishment of soft-agar colony-forming rat cell lines transformed by the adenovirus 12 E1 gene. J Virol. 1984 Jun;50(3):854–863. doi: 10.1128/jvi.50.3.854-863.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Spindler K. R., Rosser D. S., Berk A. J. Analysis of adenovirus transforming proteins from early regions 1A and 1B with antisera to inducible fusion antigens produced in Escherichia coli. J Virol. 1984 Jan;49(1):132–141. doi: 10.1128/jvi.49.1.132-141.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. Sugisaki H., Sugimoto K., Takanami M., Shiroki K., Saito I., Shimojo H., Sawada Y., Uemizu Y., Uesugi S., Fujinaga K. Structure and gene organization in the transformed Hind III-G fragment of Ad12. Cell. 1980 Jul;20(3):777–786. doi: 10.1016/0092-8674(80)90324-4. [DOI] [PubMed] [Google Scholar]
  49. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wasylyk C., Imler J. L., Wasylyk B. Transforming but not immortalizing oncogenes activate the transcription factor PEA1. EMBO J. 1988 Aug;7(8):2475–2483. doi: 10.1002/j.1460-2075.1988.tb03094.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Yang-Yen H. F., Chiu R., Karin M. Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. New Biol. 1990 Apr;2(4):351–361. [PubMed] [Google Scholar]
  52. van Dam H., Offringa R., Meijer I., Stein B., Smits A. M., Herrlich P., Bos J. L., van der Eb A. J. Differential effects of the adenovirus E1A oncogene on members of the AP-1 transcription factor family. Mol Cell Biol. 1990 Nov;10(11):5857–5864. doi: 10.1128/mcb.10.11.5857. [DOI] [PMC free article] [PubMed] [Google Scholar]

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