HTLV-1 Oncoprotein Tax and Cellular transcription Factors

  • M. Yoshida
  • T. Suzuki
  • J. Fujisawa
  • H. Hirai
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 193)


Human T cell leukemia virus (HTLV) type 1 (Poiesz et al. 1980; Yoshida et al. 1982) has two regulatory genes, tax and rex, that control the viral gene expression and replication positively and negatively (Seiki et al. 1983; Inoue et al. 1987; Hidaka et al. 1988). In these regulations, tax activates transcription of the viral genome, whereas rex modulates the processing of the viral RNA expressing unspliced forms of the viral mRNA; therefore, both regulators are indispensable for efficient viral replication.


Serum Response Factor Cellular Transcription Factor Tropical Spastic Paraparesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander C, Charnay P, Verrier B (1991) Transactivation of Krox-20 and Krox-24 promoters by the HTLV-1 fax protein through common regulatory elements. Oncogene 6: 1851–1857Google Scholar
  2. Baeuerle PA, Baltimore D (1988) Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factor. Cell 53: 211–217PubMedCrossRefGoogle Scholar
  3. Bernaud C, Lombard-Platet G, Michal Y, Jalinot P (1991) Binding of the HTLV-I Tax1 transactivator to the inducible 21 bp enhancer is mediated by the cellular factor HEB1. EMBO J 10: 3795–3803Google Scholar
  4. Bosselut R, Duvall JF, Gegonne A, Bailly M, Hemar A, Brady J (1990) The product of the c-ets-1 protooncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T-cell leukemia virus HTLV-1. EMBO J 9: 3137–3144PubMedGoogle Scholar
  5. Brady JN, Jeang K-T, Duvall J, Khoury G (1987) Identification of p40X-responsive regulatory sequences within the human T-cell leukemia virus type I long terminal repeat. J Virol 61: 2175–2181PubMedGoogle Scholar
  6. Chen ISY, Slamon DJ, Rosenblatt JD, Shah NP, Quan SG, Wachsman W (1985) The x gene is essential for HTLV replication. Science 229: 54–58PubMedCrossRefGoogle Scholar
  7. DeCaprio JA, Ludlo JW, Figge J, Shew JY, Huang CM, Lee WH, Marsilio E, Paucha E, Livingston DM (1988) SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54: 275–283PubMedCrossRefGoogle Scholar
  8. Dyson N, Howley PM, Münger K, Harlow E (1989) The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243: 934–937PubMedCrossRefGoogle Scholar
  9. Felber BK, Paskalis H, Kleinman-Ewing C, Wong-Staal F, Pavlakis GN (1985) The pX protein of HTLV-1 is a transcriptional activator of its long terminal repeats. Science 229: 675–679PubMedCrossRefGoogle Scholar
  10. Foulkes NS, Borrelli E, Sassone-Corsi P (1991) CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription. Cell 64: 739–749PubMedCrossRefGoogle Scholar
  11. Fujii M, Tsuchiya H, Chuhjo T, Akizawa T, Seiki M (1992) Interaction of HTLV-1 Taxi with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. Genes Dev 6: 2066–2076PubMedCrossRefGoogle Scholar
  12. Fujisawa J, Seiki M, Kiyokawa T, Yoshida M (1985) Functional activation of long terminal repeat of human T-cell leukemia virus type I by trans-activator. Proc Natl Acad Sci USA 82: 2277–2281PubMedCrossRefGoogle Scholar
  13. Fujisawa J, Seiki M, Sato M, Yoshida M (1986) A transcriptional enhancer of HTLV-1 is responsible for trans-activation mediated by p40x of HTLV-1. EMBO J 5: 713–718PubMedGoogle Scholar
  14. Fujisawa J, Toita M, Yoshimura T, Yoshida M (1991) The indirect association of human T-cell leukemia virus tax fusion protein with DNA results in transcriptional activation.J Virol 65: 4525–4528PubMedGoogle Scholar
  15. Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, De The G (1985) Antibodies to human T-lymphotropic virus type 1 in patients with tropical spastic paraparesis. Lancet 2: 407–410PubMedCrossRefGoogle Scholar
  16. Ghosh S, Baltimore D (1990) Activation in vitro of NF-κB by phosphorylation of its inhibitor IκB. Nature 344: 678–682PubMedCrossRefGoogle Scholar
  17. Ghosh S, Gifford AM, Rivicre LR, Tempst P, Nolan GP, Baltimore D (1990) Cloning of the p50 DNA binding subunit of NF-κB: Homology to rel and dorsal. Cell 62: 1019–1029PubMedCrossRefGoogle Scholar
  18. Gonzalez GA, Yamamoto KK, Fisher WH, Karr D, Menzel P, Biggs W III, Vale WW, Montiminy MR (1989) A cluster of phosphorylation sites on the cylic AMP-regulated nuclear factor CREB predicted by its sequence. Nature 337: 749–752PubMedCrossRefGoogle Scholar
  19. Grassman R, Dengler C, Muller-Fleckenstein I, Fleckenstein B, McGuire K, Dokhelar M, Sodroski J, Haseltine W (1989) Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector. Proc Natl Acad Sci USA 86: 3351–3355CrossRefGoogle Scholar
  20. Hai T, Liu F, Coukos WJ, Green MR (1989) Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev 3: 2083–2090PubMedCrossRefGoogle Scholar
  21. Hidaka M, Inoue M, Yoshida M, Seiki M (1988) Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. EMBO J 7: 519–523PubMedGoogle Scholar
  22. Hirai H, Fujisawa J, Suzuki T, Ueda K, Muramatsu M, Tsubol A, Arai N, Yoshida M (1992) Trans-activator tax of HTLV-1 binds to the NkB precursor p 105. Oncogene 7: 1737–1742PubMedGoogle Scholar
  23. Inoue J, Seiki M, Taniguchi T, Tsuru S, Yoshida M (1986) Induction of interleukin-2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J 5: 2883–2888PubMedGoogle Scholar
  24. Inoue J, Yoshida M, Seiki M (1987) Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type-I genes. Proc Natl Acad Sci USA 84: 3635–3657Google Scholar
  25. Jeang KT, Shank PR, Kumar A (1988) Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type 1 that proteins occur in the absence of de novo protein synthesis. Proc Natl Acad Sci USA 85: 8291–8295PubMedCrossRefGoogle Scholar
  26. Kieran M, Blank V, Logeat F, Vandekcrckhove J, Lottspeich F, Le Bail O, Urban MB, Kourisky P, Baeuerle PA, Israel A (1990) The DNA binding subunit of NF-κB is identical to factor KBF1 and homologous to the rel oncogene product. Cell 62: 1007–1018PubMedCrossRefGoogle Scholar
  27. Kinzler KW, Ruppert JM, Bigner SH, Vogelstein B (1988) The GLI gene is a member of the Kruppel family of zinc finger proteins. Nature 332: 371–374PubMedCrossRefGoogle Scholar
  28. Leung K, Nabel GJ (1988) HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-KB-like factor. Nature 333: 776–778PubMedCrossRefGoogle Scholar
  29. Lowenthal JW, Böhnlein E, Ballard DW, Greene W (1988) Regulation of interleukin-2 receptor a subunit (Tac or CD25 antigen) gene expression: binding of inducible nuclear proteins to discrete promoter sequences correlates with transcriptional activation. Proc Natl Acad Sci USA 85: 4468–4472PubMedCrossRefGoogle Scholar
  30. Marriott SJ, Lindholm PF, Brown KM, Gitlin SD, Duvall JF, Radonovich MF, Brady JN (1990) A 36-kilodalton cellular transcription factor mediates an indirect interaction of human T-cell leukemia/lymphoma virus type I TAX1 with a responsive element in the viral long terminal repeat. Mol Cell Biol 10: 4192–4201PubMedGoogle Scholar
  31. Maruyama M, Shibuya H, Harada H, Hatakeyama M, Seiki M, Fujita T, Inoue J, Yoshida M, Taniguchi T (1987) Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1 encoded by p40X and T3/T1 complex triggering. Cell 48: 493–500CrossRefGoogle Scholar
  32. Nerenberg M, Hinrichs SH, Reynolds RK, Khoury G, Jay G (1987) The tat gene of human T-lymphotropic virus type I induces mesenchymal tumors in transgenic mice. Science 237: 1324–1329PubMedCrossRefGoogle Scholar
  33. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M (1986) HTLV-1-associated myelopathy, a new clinical entity. Lancet i: 1031–1032CrossRefGoogle Scholar
  34. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980) Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci USA 77: 7415–7419PubMedCrossRefGoogle Scholar
  35. Ptashne M (1988) How eukaryotic transcriptional activators work. Nature 335: 683–689PubMedCrossRefGoogle Scholar
  36. Rice NR, MacKichan ML, Israel A (1992) The precursor of NF-κB p50 has IκB-like functions. Cell 71: 243–253PubMedCrossRefGoogle Scholar
  37. Schmitz ML, Henkel T, Baeurle PA (1991) Proteins controlling the nuclear uptake of NF-κB, Rel and dorsal. Trends Cell Biol 1: 130–137PubMedCrossRefGoogle Scholar
  38. Seiki M, Hattori S, Hirayama Y, Yoshida M (1983) Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci USA 80: 3618–3622PubMedCrossRefGoogle Scholar
  39. Shimotohno K, Takano M, Teruuchi T, Miwa M (1986) 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 USA 83: 8112–8116PubMedCrossRefGoogle Scholar
  40. Smith MR, Greene WC (1990) Identification of HTLV-1 tax trans-activator mutants exhibiting novel transcriptional phenotypes. Genes Dev 4: 1875–1885PubMedCrossRefGoogle Scholar
  41. Sodroski JC, Rosen CA, Hascltine WA (1984) Trans-acting transcriptional activation of the long terminal repeat of human T-lymphotropic viruses in infected cells. Science 226: 177–179CrossRefGoogle Scholar
  42. Suzuki T, Fujisawa J, Toita M, Yoshida M (1993a) The trans-activator tax of human T-cell leukemia virus type 1 (HTLV-1) interacts with cAMP-responsive element (CRE) binding and CRE modulator proteins that bind to the 21-base-pair enhancer of HTLV-1. Proc Natl Acad Sci USA 90: 610–614PubMedCrossRefGoogle Scholar
  43. Suzuki T, Hirai H, Fujisawa J, Fujita T, Yoshida M (1993b) A trans-activator tax of human T-cell leukemia virus type I binds to NF-κB p50 and serum response factor (SRF) and associates with enhancer DNAs of the NF-κB site and CArG box. Oncogene 8: 2391–2397PubMedGoogle Scholar
  44. Tanaka A, Takahashi C, Yamaoka S, Nosaka T, Maki M, Hatanaka M (1990) Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro. Proc Natl Acad Sci USA 87:1071–1075PubMedCrossRefGoogle Scholar
  45. Tanimura A, Teshima H, Fujisawa J, Yoshida M (1993) A new regulatory element that augments the Tax-dependent enhancer of human T-cell leukemia virus type 1 and cloning of cDNAs encoding its binding proteins. J Virol 67: 5375–5382PubMedGoogle Scholar
  46. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H (1977) Adult T-cell leukemia. Clinical and hematologic features of 16 cases. Blood 50: 481–491PubMedGoogle Scholar
  47. Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA, Harlow E (1988) Association between an oncogene and an anti-oncogene: the adenovirus EIA proteins bind to the retinoblastoma gene product. Nature 334: 124–129PubMedCrossRefGoogle Scholar
  48. Yoshida M, Miyoshi I, Hinuma Y (1982) Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the diseases. Proc Natl Acad Sci USA 79: 2031–2035PubMedCrossRefGoogle Scholar
  49. Yoshida M, Seiki M, Yamaguchi K, Takatsuki K (1984) Monoclonal integration of HTLV in all primary tumors of adult T-cell leukemia suggests causative role of HTLV in the disease. Proc Natl Acad Sci USA 81: 2534–2537PubMedCrossRefGoogle Scholar
  50. Yoshimura T, Fujisawa J, Yoshida M (1989) 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 9: 2537–2542Google Scholar
  51. Zhao L, Giam C (1991) Interaction of the human T-cell lymphotrophic virus type I (HTLV-1) transcriptional activator tax with cellular factors that bind specifically to the 21-base-pair repeats in the HTLV-1 enhancer. Proc Natl Acad Sci USA 88: 11445–11449PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • M. Yoshida
    • 1
  • T. Suzuki
    • 1
  • J. Fujisawa
    • 1
  • H. Hirai
    • 1
  1. 1.Department of Cellular and Molecular BiologyInstitute of Medical Science, The University of TokyoTokyoJapan

Personalised recommendations