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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
. 1993 Aug 1;90(15):7303–7307. doi: 10.1073/pnas.90.15.7303

Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors.

A P Armstrong 1, A A Franklin 1, M N Uittenbogaard 1, H A Giebler 1, J K Nyborg 1
PMCID: PMC47125  PMID: 8346248

Abstract

The Tax protein, encoded by the human T-cell leukemia virus type I, is a potent activator of viral and cellular gene transcription. Tax does not bind DNA directly but appears to trans-activate through an interaction with host-cell transcription factors that recognize sequences within the promoters of Tax-responsive genes. Cellular transcriptional activators implicated in mediating Tax trans-activation include members of the activating transcription factor/cAMP response element binding protein (ATF/CREB) family of proteins, serum response factor, Fos-Jun, and NF-kappa B. Recent evidence suggests that Tax may stimulate human T-cell leukemia virus type I transcription, at least in part, through enhanced binding of ATF/CREB proteins to their recognition elements within the Tax-responsive 21-bp repeats of the viral promoter. In this report, we demonstrate that Tax also enhances the site-specific DNA binding activity of serum response factor and Fos-Jun and modestly enhances the binding of the NF-kappa B subunits, p50 and p65. We also show that Tax increases the DNA binding activity of the eukaryotic transcription factors ATF-1, Sp1, and GAL4. These results are consistent with the finding that Tax is highly pleiotropic and suggest that Tax trans-activation may involve enhancement in the DNA binding activity of target transcriptional regulatory proteins. In addition, we show that the mechanism of Tax-enhanced DNA binding activity does not involve an alteration in the redox state of the target protein.

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Selected References

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  1. Abate C., Luk D., Gentz R., Rauscher F. J., 3rd, Curran T. Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1032–1036. doi: 10.1073/pnas.87.3.1032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abate C., Patel L., Rauscher F. J., 3rd, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science. 1990 Sep 7;249(4973):1157–1161. doi: 10.1126/science.2118682. [DOI] [PubMed] [Google Scholar]
  3. Alexandre C., Charnay P., Verrier B. Transactivation of Krox-20 and Krox-24 promoters by the HTLV-1 Tax protein through common regulatory elements. Oncogene. 1991 Oct;6(10):1851–1857. [PubMed] [Google Scholar]
  4. Alexandre C., Verrier B. Four regulatory elements in the human c-fos promoter mediate transactivation by HTLV-1 Tax protein. Oncogene. 1991 Apr;6(4):543–551. [PubMed] [Google Scholar]
  5. Arima N., Molitor J. A., Smith M. R., Kim J. H., Daitoku Y., Greene W. C. Human T-cell leukemia virus type I Tax induces expression of the Rel-related family of kappa B enhancer-binding proteins: evidence for a pretranslational component of regulation. J Virol. 1991 Dec;65(12):6892–6899. doi: 10.1128/jvi.65.12.6892-6899.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ballard D. W., Böhnlein E., Lowenthal J. W., Wano Y., Franza B. R., Greene W. C. HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene. Science. 1988 Sep 23;241(4873):1652–1655. doi: 10.1126/science.241.4873.1652. [DOI] [PubMed] [Google Scholar]
  7. Beimling P., Moelling K. Direct interaction of CREB protein with 21 bp Tax-response elements of HTLV-ILTR. Oncogene. 1992 Feb;7(2):257–262. [PubMed] [Google Scholar]
  8. Böhnlein E., Siekevitz M., Ballard D. W., Lowenthal J. W., Rimsky L., Bogérd H., Hoffman J., Wano Y., Franza B. R., Greene W. C. Stimulation of the human immunodeficiency virus type 1 enhancer by the human T-cell leukemia virus type I tax gene product involves the action of inducible cellular proteins. J Virol. 1989 Apr;63(4):1578–1586. doi: 10.1128/jvi.63.4.1578-1586.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cann A. J., Rosenblatt J. D., Wachsman W., Shah N. P., Chen I. S. Identification of the gene responsible for human T-cell leukaemia virus transcriptional regulation. Nature. 1985 Dec 12;318(6046):571–574. doi: 10.1038/318571a0. [DOI] [PubMed] [Google Scholar]
  10. Chen I. S., Slamon D. J., Rosenblatt J. D., Shah N. P., Quan S. G., Wachsman W. The x gene is essential for HTLV replication. Science. 1985 Jul 5;229(4708):54–58. doi: 10.1126/science.2990037. [DOI] [PubMed] [Google Scholar]
  11. Felber B. K., Paskalis H., Kleinman-Ewing C., Wong-Staal F., Pavlakis G. N. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985 Aug 16;229(4714):675–679. doi: 10.1126/science.2992082. [DOI] [PubMed] [Google Scholar]
  12. Fujii M., Niki T., Mori T., Matsuda T., Matsui M., Nomura N., Seiki M. HTLV-1 Tax induces expression of various immediate early serum responsive genes. Oncogene. 1991 Jun;6(6):1023–1029. [PubMed] [Google Scholar]
  13. Fujii M., Tsuchiya H., Chuhjo T., Akizawa T., Seiki M. Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. Genes Dev. 1992 Nov;6(11):2066–2076. doi: 10.1101/gad.6.11.2066. [DOI] [PubMed] [Google Scholar]
  14. Fujisawa J., Seiki M., Sato M., Yoshida M. A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I. EMBO J. 1986 Apr;5(4):713–718. doi: 10.1002/j.1460-2075.1986.tb04272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grueneberg D. A., Natesan S., Alexandre C., Gilman M. Z. Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor. Science. 1992 Aug 21;257(5073):1089–1095. doi: 10.1126/science.257.5073.1089. [DOI] [PubMed] [Google Scholar]
  16. Hoeffler J. P., Lustbader J. W., Chen C. Y. Identification of multiple nuclear factors that interact with cyclic adenosine 3',5'-monophosphate response element-binding protein and activating transcription factor-2 by protein-protein interactions. Mol Endocrinol. 1991 Feb;5(2):256–266. doi: 10.1210/mend-5-2-256. [DOI] [PubMed] [Google Scholar]
  17. Kim S. J., Kehrl J. H., Burton J., Tendler C. L., Jeang K. T., Danielpour D., Thevenin C., Kim K. Y., Sporn M. B., Roberts A. B. Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia. J Exp Med. 1990 Jul 1;172(1):121–129. doi: 10.1084/jem.172.1.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leung K., Nabel G. J. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor. Nature. 1988 Jun 23;333(6175):776–778. doi: 10.1038/333776a0. [DOI] [PubMed] [Google Scholar]
  19. Marriott S. J., Boros I., Duvall J. F., Brady J. N. Indirect binding of human T-cell leukemia virus type I tax1 to a responsive element in the viral long terminal repeat. Mol Cell Biol. 1989 Oct;9(10):4152–4160. doi: 10.1128/mcb.9.10.4152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Matthews M. A., Markowitz R. B., Dynan W. S. In vitro activation of transcription by the human T-cell leukemia virus type I Tax protein. Mol Cell Biol. 1992 May;12(5):1986–1996. doi: 10.1128/mcb.12.5.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nyborg J. K., Dynan W. S., Chen I. S., Wachsman W. Binding of host-cell factors to DNA sequences in the long terminal repeat of human T-cell leukemia virus type I: implications for viral gene expression. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1457–1461. doi: 10.1073/pnas.85.5.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nyborg J. K., Matthews M. A., Yucel J., Walls L., Golde W. T., Dynan W. S., Wachsman W. Interaction of host cell proteins with the human T-cell leukemia virus type I transcriptional control region. II. A comprehensive map of protein-binding sites facilitates construction of a simple chimeric promoter responsive to the viral tax2 gene product. J Biol Chem. 1990 May 15;265(14):8237–8242. [PubMed] [Google Scholar]
  23. Paskalis H., Felber B. K., Pavlakis G. N. Cis-acting sequences responsible for the transcriptional activation of human T-cell leukemia virus type I constitute a conditional enhancer. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6558–6562. doi: 10.1073/pnas.83.17.6558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ruben S. M., Narayanan R., Klement J. F., Chen C. H., Rosen C. A. Functional characterization of the NF-kappa B p65 transcriptional activator and an alternatively spliced derivative. Mol Cell Biol. 1992 Feb;12(2):444–454. doi: 10.1128/mcb.12.2.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ruben S., Poteat H., Tan T. H., Kawakami K., Roeder R., Haseltine W., Rosen C. A. Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product. Science. 1988 Jul 1;241(4861):89–92. doi: 10.1126/science.2838905. [DOI] [PubMed] [Google Scholar]
  26. Semmes O. J., Jeang K. T. Mutational analysis of human T-cell leukemia virus type I Tax: regions necessary for function determined with 47 mutant proteins. J Virol. 1992 Dec;66(12):7183–7192. doi: 10.1128/jvi.66.12.7183-7192.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shimotohno K., Takano M., Teruuchi T., Miwa M. Requirement of multiple copies of a 21-nucleotide sequence in the U3 regions of human T-cell leukemia virus type I and type II long terminal repeats for trans-acting activation of transcription. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8112–8116. doi: 10.1073/pnas.83.21.8112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Siekevitz M., Josephs S. F., Dukovich M., Peffer N., Wong-Staal F., Greene W. C. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Science. 1987 Dec 11;238(4833):1575–1578. doi: 10.1126/science.2825351. [DOI] [PubMed] [Google Scholar]
  29. Smith M. R., Greene W. C. Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes. Genes Dev. 1990 Nov;4(11):1875–1885. doi: 10.1101/gad.4.11.1875. [DOI] [PubMed] [Google Scholar]
  30. Sodroski J. G., Rosen C. A., Haseltine W. A. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
  31. Xanthoudakis S., Miao G., Wang F., Pan Y. C., Curran T. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J. 1992 Sep;11(9):3323–3335. doi: 10.1002/j.1460-2075.1992.tb05411.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yoshimura T., Fujisawa J., Yoshida M. Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. EMBO J. 1990 Aug;9(8):2537–2542. doi: 10.1002/j.1460-2075.1990.tb07434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zhao L. J., Giam C. Z. Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7070–7074. doi: 10.1073/pnas.89.15.7070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zhao L. J., Giam C. Z. Interaction of the human T-cell lymphotrophic virus type I (HTLV-I) transcriptional activator Tax with cellular factors that bind specifically to the 21-base-pair repeats in the HTLV-I enhancer. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11445–11449. doi: 10.1073/pnas.88.24.11445. [DOI] [PMC free article] [PubMed] [Google Scholar]

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