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Journal of Virology logoLink to Journal of Virology
. 1996 Aug;70(8):5194–5202. doi: 10.1128/jvi.70.8.5194-5202.1996

The tax gene of human T-cell leukemia virus type 2 is essential for transformation of human T lymphocytes.

T M Ross 1, S M Pettiford 1, P L Green 1
PMCID: PMC190475  PMID: 8764028

Abstract

The mechanism of human T-cell leukemia virus (HTLV)-mediated transformation and induction of malignancy is unknown; however, several studies have implicated the viral gene product, Tax. Conclusive evidence for the role of Tax in the HTLV malignant process has been impeded by the inability to mutate tax in the context of an infectious virus and dissociate viral replication from cellular transformation. To circumvent this problem we constructed a mutant of HTLV type 2 (HTLV-2) that replicates by a Tax-independent mechanism. For these studies, the Tax response element in the viral long terminal repeat was replaced with the cytomegalovirus immediate-early promoter enhancer (C-enh). Transcription of the chimeric HTLV-2 (HTLVC-enh) was efficiently directed by this heterologous promoter. Also, the chimeric virus transformed primary human T lymphocytes with an efficiency similar to that of wild-type HTLV-2. A tax-knockout virus, termed HTLVC-enhDeltaTax, was constructed to directly assess the importance of Tax in cellular transformation. Transfection and infection studies indicated that HTLVC-enhDeltaTax was replication competent; however, HTLVC-enhDeltaTax failed to transform primary human T lymphocytes. We conclude that Tax is essential for HTLV-mediated transformation of human T lymphocytes. Furthermore, this chimeric HTLV, that replicates in the absence of Tax, should facilitate studies to determine the precise mechanism of T-lymphocyte transformation by HTLV.

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Selected References

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  1. Adya N., Zhao L. J., Huang W., Boros I., Giam C. Z. Expansion of CREB's DNA recognition specificity by Tax results from interaction with Ala-Ala-Arg at positions 282-284 near the conserved DNA-binding domain of CREB. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5642–5646. doi: 10.1073/pnas.91.12.5642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. 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]
  5. Bieberich C. J., King C. M., Tinkle B. T., Jay G. A transgenic model of transactivation by the Tax protein of HTLV-I. Virology. 1993 Sep;196(1):309–318. doi: 10.1006/viro.1993.1481. [DOI] [PubMed] [Google Scholar]
  6. Boshart M., Weber F., Jahn G., Dorsch-Häsler K., Fleckenstein B., Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. doi: 10.1016/s0092-8674(85)80025-8. [DOI] [PubMed] [Google Scholar]
  7. Brady J., Jeang K. T., Duvall J., Khoury G. Identification of p40x-responsive regulatory sequences within the human T-cell leukemia virus type I long terminal repeat. J Virol. 1987 Jul;61(7):2175–2181. doi: 10.1128/jvi.61.7.2175-2181.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brockman J. A., Scherer D. C., McKinsey T. A., Hall S. M., Qi X., Lee W. Y., Ballard D. W. Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation. Mol Cell Biol. 1995 May;15(5):2809–2818. doi: 10.1128/mcb.15.5.2809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Böhnlein E., Lowenthal J. W., Siekevitz M., Ballard D. W., Franza B. R., Greene W. C. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Cell. 1988 Jun 3;53(5):827–836. doi: 10.1016/0092-8674(88)90099-2. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Chen I. S., Cann A. J., Shah N. P., Gaynor R. B. Functional relation between HTLV-II x and adenovirus E1A proteins in transcriptional activation. Science. 1985 Nov 1;230(4725):570–573. doi: 10.1126/science.2996140. [DOI] [PubMed] [Google Scholar]
  13. Chen I. S., McLaughlin J., Gasson J. C., Clark S. C., Golde D. W. Molecular characterization of genome of a novel human T-cell leukaemia virus. Nature. 1983 Oct 6;305(5934):502–505. doi: 10.1038/305502a0. [DOI] [PubMed] [Google Scholar]
  14. Chen I. S., Quan S. G., Golde D. W. Human T-cell leukemia virus type II transforms normal human lymphocytes. Proc Natl Acad Sci U S A. 1983 Nov;80(22):7006–7009. doi: 10.1073/pnas.80.22.7006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cross S. L., Feinberg M. B., Wolf J. B., Holbrook N. J., Wong-Staal F., Leonard W. J. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cell. 1987 Apr 10;49(1):47–56. doi: 10.1016/0092-8674(87)90754-9. [DOI] [PubMed] [Google Scholar]
  16. Dodon M. D., Bernard A., Gazzolo L. Peripheral T-lymphocyte activation by human T-cell leukemia virus type I interferes with the CD2 but not with the CD3/TCR pathway. J Virol. 1989 Dec;63(12):5413–5419. doi: 10.1128/jvi.63.12.5413-5419.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Fujii M., Sassone-Corsi P., Verma I. M. c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8526–8530. doi: 10.1073/pnas.85.22.8526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Fujisawa J., Seiki M., Kiyokawa T., Yoshida M. Functional activation of the long terminal repeat of human T-cell leukemia virus type I by a trans-acting factor. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2277–2281. doi: 10.1073/pnas.82.8.2277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Grassmann R., Berchtold S., Radant I., Alt M., Fleckenstein B., Sodroski J. G., Haseltine W. A., Ramstedt U. Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture. J Virol. 1992 Jul;66(7):4570–4575. doi: 10.1128/jvi.66.7.4570-4575.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Grassmann R., Dengler C., Müller-Fleckenstein I., Fleckenstein B., McGuire K., Dokhelar M. C., Sodroski J. G., Haseltine W. A. 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 U S A. 1989 May;86(9):3351–3355. doi: 10.1073/pnas.86.9.3351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Green J. E., Begley C. G., Wagner D. K., Waldmann T. A., Jay G. trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene. Mol Cell Biol. 1989 Nov;9(11):4731–4737. doi: 10.1128/mcb.9.11.4731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Green P. L., Kaehler D. A., Bennett L. M., Risser R. Multiple steps are required for the induction of tumors by Abelson murine leukemia virus. J Virol. 1989 May;63(5):1989–1994. doi: 10.1128/jvi.63.5.1989-1994.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Green P. L., Ross T. M., Chen I. S., Pettiford S. Human T-cell leukemia virus type II nucleotide sequences between env and the last exon of tax/rex are not required for viral replication or cellular transformation. J Virol. 1995 Jan;69(1):387–394. doi: 10.1128/jvi.69.1.387-394.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Green P. L., Xie Y. M., Chen I. S. The internal methionine codons of human T-cell leukemia virus type II rex gene are not required for p24rex production or virus replication and transformation. J Virol. 1990 Oct;64(10):4914–4921. doi: 10.1128/jvi.64.10.4914-4921.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Grossman W. J., Kimata J. T., Wong F. H., Zutter M., Ley T. J., Ratner L. Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1057–1061. doi: 10.1073/pnas.92.4.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ijichi S., Ramundo M. B., Takahashi H., Hall W. W. In vivo cellular tropism of human T cell leukemia virus type II (HTLV-II). J Exp Med. 1992 Jul 1;176(1):293–296. doi: 10.1084/jem.176.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Inoue J., Seiki M., Taniguchi T., Tsuru S., Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. doi: 10.1002/j.1460-2075.1986.tb04583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Jeang K. T., Boros I., Brady J., Radonovich M., Khoury G. Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence. J Virol. 1988 Dec;62(12):4499–4509. doi: 10.1128/jvi.62.12.4499-4509.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jeang K. T., Chiu R., Santos E., Kim S. J. Induction of the HTLV-I LTR by Jun occurs through the Tax-responsive 21-bp elements. Virology. 1991 Mar;181(1):218–227. doi: 10.1016/0042-6822(91)90487-v. [DOI] [PubMed] [Google Scholar]
  34. Jeang K. T., Shank P. R., Kumar A. Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type I tat proteins occurs in the absence of de novo protein synthesis. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8291–8295. doi: 10.1073/pnas.85.21.8291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jeang K. T., Widen S. G., Semmes O. J., 4th, Wilson S. H. HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta-polymerase gene. Science. 1990 Mar 2;247(4946):1082–1084. doi: 10.1126/science.2309119. [DOI] [PubMed] [Google Scholar]
  36. Kanno T., Brown K., Franzoso G., Siebenlist U. Kinetic analysis of human T-cell leukemia virus type I Tax-mediated activation of NF-kappa B. Mol Cell Biol. 1994 Oct;14(10):6443–6451. doi: 10.1128/mcb.14.10.6443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kimata J. T., Palker T. J., Ratner L. The mitogenic activity of human T-cell leukemia virus type I is T-cell associated and requires the CD2/LFA-3 activation pathway. J Virol. 1993 Jun;67(6):3134–3141. doi: 10.1128/jvi.67.6.3134-3141.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kimata J. T., Ratner L. Temporal regulation of viral and cellular gene expression during human T-lymphotropic virus type I-mediated lymphocyte immortalization. J Virol. 1991 Aug;65(8):4398–4407. doi: 10.1128/jvi.65.8.4398-4407.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lal R. B., Owen S. M., Rudolph D. L., Dawson C., Prince H. In vivo cellular tropism of human T-lymphotropic virus type II is not restricted to CD8+ cells. Virology. 1995 Jul 10;210(2):441–447. doi: 10.1006/viro.1995.1360. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Maguer V., Cassé-Ripoll H., Gazzolo L., Dodon M. D. Human T-cell leukemia virus type I-induced proliferation of human immature CD2+CD3- thymocytes. J Virol. 1993 Sep;67(9):5529–5537. doi: 10.1128/jvi.67.9.5529-5537.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Maruyama M., Shibuya H., Harada H., Hatakeyama M., Seiki M., Fujita T., Inoue J., Yoshida M., Taniguchi T. Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering. Cell. 1987 Jan 30;48(2):343–350. doi: 10.1016/0092-8674(87)90437-5. [DOI] [PubMed] [Google Scholar]
  43. McKinsey T. A., Brockman J. A., Scherer D. C., Al-Murrani S. W., Green P. L., Ballard D. W. Inactivation of IkappaBbeta by the tax protein of human T-cell leukemia virus type 1: a potential mechanism for constitutive induction of NF-kappaB. Mol Cell Biol. 1996 May;16(5):2083–2090. doi: 10.1128/mcb.16.5.2083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Miyamoto K., Kamiya T., Minowada J., Tomita N., Kitajima K. Transformation of CD8+ T-cells producing a strong cytopathic effect on CD4+ T-cells through syncytium formation by HTLV-II. Jpn J Cancer Res. 1991 Nov;82(11):1178–1183. doi: 10.1111/j.1349-7006.1991.tb01775.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Nagata K., Ohtani K., Nakamura M., Sugamura K. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40tax protein in the human T-cell line, Jurkat. J Virol. 1989 Aug;63(8):3220–3226. doi: 10.1128/jvi.63.8.3220-3226.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Nerenberg M. I., Minor T., Price J., Ernst D. N., Shinohara T., Schwarz H. Transgenic thymocytes are refractory to transformation by the human T-cell leukemia virus type I tax gene. J Virol. 1991 Jun;65(6):3349–3353. doi: 10.1128/jvi.65.6.3349-3353.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Nerenberg M., Hinrichs S. H., Reynolds R. K., Khoury G., Jay G. The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice. Science. 1987 Sep 11;237(4820):1324–1329. doi: 10.1126/science.2888190. [DOI] [PubMed] [Google Scholar]
  48. Nimer S. D., Gasson J. C., Hu K., Smalberg I., Williams J. L., Chen I. S., Rosenblatt J. D. Activation of the GM-CSF promoter by HTLV-I and -II tax proteins. Oncogene. 1989 Jun;4(6):671–676. [PubMed] [Google Scholar]
  49. Nimer S. Tax responsiveness of the GM-CSF promoter is mediated by mitogen-inducible sequences other than kappa B. New Biol. 1991 Oct;3(10):997–1004. [PubMed] [Google Scholar]
  50. 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]
  51. Rosen C. A., Park R., Sodroski J. G., Haseltine W. A. Multiple sequence elements are required for regulation of human T-cell leukemia virus gene expression. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4919–4923. doi: 10.1073/pnas.84.14.4919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Rosenblatt J. D., Cann A. J., Slamon D. J., Smalberg I. S., Shah N. P., Fujii J., Wachsman W., Chen I. S. HTLV-II transactivation is regulated by the overlapping tax/rex nonstructural genes. Science. 1988 May 13;240(4854):916–919. doi: 10.1126/science.2834826. [DOI] [PubMed] [Google Scholar]
  53. Schneider U., Schwenk H. U., Bornkamm G. Characterization of EBV-genome negative "null" and "T" cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non-Hodgkin lymphoma. Int J Cancer. 1977 May 15;19(5):621–626. doi: 10.1002/ijc.2910190505. [DOI] [PubMed] [Google Scholar]
  54. Seiki M., Inoue J., Takeda T., Yoshida M. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator. EMBO J. 1986 Mar;5(3):561–565. doi: 10.1002/j.1460-2075.1986.tb04247.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Shimotohno K., Takahashi Y., Shimizu N., Gojobori T., Golde D. W., Chen I. S., Miwa M., Sugimura T. Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. Proc Natl Acad Sci U S A. 1985 May;82(10):3101–3105. doi: 10.1073/pnas.82.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Siekevitz M., Feinberg M. B., Holbrook N., Wong-Staal F., Greene W. C. Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5389–5393. doi: 10.1073/pnas.84.15.5389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. 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]
  58. Siomi H., Shida H., Nam S. H., Nosaka T., Maki M., Hatanaka M. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell. 1988 Oct 21;55(2):197–209. doi: 10.1016/0092-8674(88)90043-8. [DOI] [PubMed] [Google Scholar]
  59. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  60. Suzuki T., Fujisawa J. I., Toita M., Yoshida M. 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 U S A. 1993 Jan 15;90(2):610–614. doi: 10.1073/pnas.90.2.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Suzuki T., Hirai H., Fujisawa J., Fujita T., Yoshida M. A trans-activator Tax of human T-cell leukemia virus type 1 binds to NF-kappa B p50 and serum response factor (SRF) and associates with enhancer DNAs of the NF-kappa B site and CArG box. Oncogene. 1993 Sep;8(9):2391–2397. [PubMed] [Google Scholar]
  62. Tanaka A., Takahashi C., Yamaoka S., Nosaka T., Maki M., Hatanaka M. Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1071–1075. doi: 10.1073/pnas.87.3.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wagner S., Green M. R. HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. Science. 1993 Oct 15;262(5132):395–399. doi: 10.1126/science.8211160. [DOI] [PubMed] [Google Scholar]
  64. Wano Y., Feinberg M., Hosking J. B., Bogerd H., Greene W. C. Stable expression of the tax gene of type I human T-cell leukemia virus in human T cells activates specific cellular genes involved in growth. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9733–9737. doi: 10.1073/pnas.85.24.9733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Yin M. J., Paulssen E. J., Seeler J. S., Gaynor R. B. Protein domains involved in both in vivo and in vitro interactions between human T-cell leukemia virus type I tax and CREB. J Virol. 1995 Jun;69(6):3420–3432. doi: 10.1128/jvi.69.6.3420-3432.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. 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]
  67. 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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