Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1993 Sep;67(9):5375–5382. doi: 10.1128/jvi.67.9.5375-5382.1993

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.

A Tanimura 1, H Teshima 1, J Fujisawa 1, M Yoshida 1
PMCID: PMC237938  PMID: 8350401

Abstract

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) trans activates the 21-bp enhancer of HTLV-1. A sequence of more than two copies of the 21-bp enhancer is efficiently activated by Tax, but one copy is not activated extensively. Another sequence (TRE-2, positions -163 to -117) adjacent to the 21-bp enhancer in the long terminal repeat of HTLV-1 can enhance a single copy of the 21-bp enhancer activity in trans activation by Tax. This sequence contains motifs related to the Ets- and NF-kappa B-binding sequences, but mutations at these sites indicated that neither is responsive to cooperation with the 21-bp enhancer. A deletion mutation of TRE-2 identified 25 bases at positions -158 to -134 (TRE-2S) as an essential sequence, and TRE-2S was sufficient to give maximum cooperation with one copy of the 21-bp enhancer in trans activation by Tax protein. Using TRE-2S as a probe, we screened a cDNA library of HUT102 cells by the Southwestern (DNA-protein) procedure and isolated two cDNA clones, THP-1 and -2. These two clones encode TRE-2S-binding proteins, and they differ by only an extra 17 amino acids in THP-2. Both THP proteins contain five zinc finger motifs which are strikingly similar to those of the GLI family, an amplified gene product in glyoma cells. The binding site of THP-1 and -2 was GAACCACCCA in TRE-2S, which is highly homologous to the GLI-binding site. These results suggest that binding of THP to TRE-2S may be involved in cooperation with one copy of the 21-bp enhancer in responding to Tax trans activation.

Full text

PDF
5378

Images in this article

Selected References

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

  1. Berg J. M. Potential metal-binding domains in nucleic acid binding proteins. Science. 1986 Apr 25;232(4749):485–487. doi: 10.1126/science.2421409. [DOI] [PubMed] [Google Scholar]
  2. Bosselut R., Duvall J. F., Gégonne A., Bailly M., Hémar A., Brady J., Ghysdael J. The product of the c-ets-1 proto-oncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV-1. EMBO J. 1990 Oct;9(10):3137–3144. doi: 10.1002/j.1460-2075.1990.tb07511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bosselut R., Lim F., Romond P. C., Frampton J., Brady J., Ghysdael J. Myb protein binds to multiple sites in the human T cell lymphotropic virus type 1 long terminal repeat and transactivates LTR-mediated expression. Virology. 1992 Feb;186(2):764–769. doi: 10.1016/0042-6822(92)90044-p. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Béraud C., Lombard-Platet G., Michal Y., Jalinot P. Binding of the HTLV-I Tax1 transactivator to the inducible 21 bp enhancer is mediated by the cellular factor HEB1. EMBO J. 1991 Dec;10(12):3795–3803. doi: 10.1002/j.1460-2075.1991.tb04949.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. Fujisawa J., Toita M., Yoshida M. A unique enhancer element for the trans activator (p40tax) of human T-cell leukemia virus type I that is distinct from cyclic AMP- and 12-O-tetradecanoylphorbol-13-acetate-responsive elements. J Virol. 1989 Aug;63(8):3234–3239. doi: 10.1128/jvi.63.8.3234-3239.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fujisawa J., Toita M., Yoshimura T., Yoshida M. The indirect association of human T-cell leukemia virus tax protein with DNA results in transcriptional activation. J Virol. 1991 Aug;65(8):4525–4528. doi: 10.1128/jvi.65.8.4525-4528.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gitlin S. D., Bosselut R., Gégonne A., Ghysdael J., Brady J. N. Sequence-specific interaction of the Ets1 protein with the long terminal repeat of the human T-lymphotropic virus type I. J Virol. 1991 Oct;65(10):5513–5523. doi: 10.1128/jvi.65.10.5513-5523.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gégonne A., Bosselut R., Bailly R. A., Ghysdael J. Synergistic activation of the HTLV1 LTR Ets-responsive region by transcription factors Ets1 and Sp1. EMBO J. 1993 Mar;12(3):1169–1178. doi: 10.1002/j.1460-2075.1993.tb05758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Kinzler K. W., Bigner S. H., Bigner D. D., Trent J. M., Law M. L., O'Brien S. J., Wong A. J., Vogelstein B. Identification of an amplified, highly expressed gene in a human glioma. Science. 1987 Apr 3;236(4797):70–73. doi: 10.1126/science.3563490. [DOI] [PubMed] [Google Scholar]
  19. Kinzler K. W., Vogelstein B. The GLI gene encodes a nuclear protein which binds specific sequences in the human genome. Mol Cell Biol. 1990 Feb;10(2):634–642. doi: 10.1128/mcb.10.2.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Lowenthal J. W., Böhnlein E., Ballard D. W., Greene W. C. Regulation of interleukin 2 receptor alpha subunit (Tac or CD25 antigen) gene expression: binding of inducible nuclear proteins to discrete promoter sequences correlates with transcriptional activation. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4468–4472. doi: 10.1073/pnas.85.12.4468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Manley J. L., Fire A., Samuels M., Sharp P. A. In vitro transcription: whole-cell extract. Methods Enzymol. 1983;101:568–582. doi: 10.1016/0076-6879(83)01038-1. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Marriott S. J., Lindholm P. F., Brown K. M., Gitlin S. D., Duvall J. F., Radonovich M. F., Brady J. N. 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. 1990 Aug;10(8):4192–4201. doi: 10.1128/mcb.10.8.4192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miller J., McLachlan A. D., Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985 Jun;4(6):1609–1614. doi: 10.1002/j.1460-2075.1985.tb03825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miyatake S., Seiki M., Malefijt R. D., Heike T., Fujisawa J., Takebe Y., Nishida J., Shlomai J., Yokota T., Yoshida M. Activation of T cell-derived lymphokine genes in T cells and fibroblasts: effects of human T cell leukemia virus type I p40x protein and bovine papilloma virus encoded E2 protein. Nucleic Acids Res. 1988 Jul 25;16(14A):6547–6566. doi: 10.1093/nar/16.14.6547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Numata N., Ohtani K., Niki M., Nakamura M., Sugamura K. Synergism between two distinct elements of the HTLV-I enhancer during activation by the trans-activator of HTLV-I. New Biol. 1991 Sep;3(9):896–906. [PubMed] [Google Scholar]
  28. 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]
  29. Orenic T. V., Slusarski D. C., Kroll K. L., Holmgren R. A. Cloning and characterization of the segment polarity gene cubitus interruptus Dominant of Drosophila. Genes Dev. 1990 Jun;4(6):1053–1067. doi: 10.1101/gad.4.6.1053. [DOI] [PubMed] [Google Scholar]
  30. Park R. E., Haseltine W. A., Rosen C. A. A nuclear factor is required for transactivation of HTLV-I gene expression. Oncogene. 1988 Sep;3(3):275–279. [PubMed] [Google Scholar]
  31. 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]
  32. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. 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 U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ruppert J. M., Vogelstein B., Kinzler K. W. The zinc finger protein GLI transforms primary cells in cooperation with adenovirus E1A. Mol Cell Biol. 1991 Mar;11(3):1724–1728. doi: 10.1128/mcb.11.3.1724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ruppert J. M., Vogelstein B., Kinzler K. W. The zinc finger protein GLI transforms primary cells in cooperation with adenovirus E1A. Mol Cell Biol. 1991 Mar;11(3):1724–1728. doi: 10.1128/mcb.11.3.1724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. 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]
  37. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Yoshida M., Miyoshi I., Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. doi: 10.1073/pnas.79.6.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yoshida M., Seiki M., Yamaguchi K., Takatsuki K. Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2534–2537. doi: 10.1073/pnas.81.8.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Zarkower D., Hodgkin J. Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Cell. 1992 Jul 24;70(2):237–249. doi: 10.1016/0092-8674(92)90099-x. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. 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]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES