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. 1989 Oct;9(10):4152–4160. doi: 10.1128/mcb.9.10.4152

Indirect binding of human T-cell leukemia virus type I tax1 to a responsive element in the viral long terminal repeat.

S J Marriott 1, I Boros 1, J F Duvall 1, J N Brady 1
PMCID: PMC362493  PMID: 2555684

Abstract

Several laboratories have demonstrated that tandem copies of the human T-cell leukemia virus type I 21-base-pair (bp) repeat cloned upstream of either a homologous or heterologous promoter increase transcription in the presence of tax1 protein. In this report, we provide evidence for a second tax1-responsive sequence in the viral long terminal repeat. Analysis of human T-cell leukemia virus type I promoter deletion mutants and plasmids containing cloned oligonucleotide motifs demonstrated that this 47-bp sequence, located between -117 and -163, confers responsiveness to tax1. We further demonstrated that proteins present in HeLa nuclear extracts bind specifically to this tax1-responsive sequence. Mutants that affected in vivo activity also decreased in vitro binding. Using an in vitro binding assay, we demonstrated that tax1 interacts indirectly with the 47-bp sequence, most likely through protein-protein interaction. Thus, while tax1 does not bind directly to DNA to enhance transcription, it may influence sequence-specific responses by interacting with the primary DNA-protein complex.

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Selected References

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  1. Abmayr S. M., Workman J. L., Roeder R. G. The pseudorabies immediate early protein stimulates in vitro transcription by facilitating TFIID: promoter interactions. Genes Dev. 1988 May;2(5):542–553. doi: 10.1101/gad.2.5.542. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. 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]
  5. DeCaprio J. A., Ludlow J. W., Figge J., Shew J. Y., Huang C. M., Lee W. H., Marsilio E., Paucha E., Livingston D. M. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988 Jul 15;54(2):275–283. doi: 10.1016/0092-8674(88)90559-4. [DOI] [PubMed] [Google Scholar]
  6. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Franza B. R., Jr, Rauscher F. J., 3rd, Josephs S. F., Curran T. The Fos complex and Fos-related antigens recognize sequence elements that contain AP-1 binding sites. Science. 1988 Mar 4;239(4844):1150–1153. doi: 10.1126/science.2964084. [DOI] [PubMed] [Google Scholar]
  8. Fried M., Crothers D. M. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. doi: 10.1093/nar/9.23.6505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gallo R., Wong-Staal F., Montagnier L., Haseltine W. A., Yoshida M. HIV/HTLV gene nomenclature. Nature. 1988 Jun 9;333(6173):504–504. doi: 10.1038/333504a0. [DOI] [PubMed] [Google Scholar]
  10. Garner M. M., Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981 Jul 10;9(13):3047–3060. doi: 10.1093/nar/9.13.3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goh W. C., Sodroski J., Rosen C., Essex M., Haseltine W. A. Subcellular localization of the product of the long open reading frame of human T-cell leukemia virus type I. Science. 1985 Mar 8;227(4691):1227–1228. doi: 10.1126/science.2983419. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Haseltine W. A., Sodroski J., Patarca R., Briggs D., Perkins D., Wong-Staal F. Structure of 3' terminal region of type II human T lymphotropic virus: evidence for new coding region. Science. 1984 Jul 27;225(4660):419–421. doi: 10.1126/science.6330894. [DOI] [PubMed] [Google Scholar]
  14. Hinrichs S. H., Nerenberg M., Reynolds R. K., Khoury G., Jay G. A transgenic mouse model for human neurofibromatosis. Science. 1987 Sep 11;237(4820):1340–1343. doi: 10.1126/science.2888191. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Jeang K. T., Giam C. Z., Nerenberg M., Khoury G. Abundant synthesis of functional human T-cell leukemia virus type I p40x protein in eucaryotic cells by using a baculovirus expression vector. J Virol. 1987 Mar;61(3):708–713. doi: 10.1128/jvi.61.3.708-713.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Kiyokawa T., Kawaguchi T., Seiki M., Yoshida M. Association of the pX gene product of human T-cell leukemia virus type-I with nucleus. Virology. 1985 Dec;147(2):462–465. doi: 10.1016/0042-6822(85)90149-7. [DOI] [PubMed] [Google Scholar]
  19. Kiyokawa T., Seiki M., Imagawa K., Shimizu F., Yoshida M. Identification of a protein (p40x) encoded by a unique sequence pX of human T-cell leukemia virus type I. Gan. 1984 Sep;75(9):747–751. [PubMed] [Google Scholar]
  20. Kouzarides T., Ziff E. The role of the leucine zipper in the fos-jun interaction. Nature. 1988 Dec 15;336(6200):646–651. doi: 10.1038/336646a0. [DOI] [PubMed] [Google Scholar]
  21. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
  22. Lee T. H., Coligan J. E., Sodroski J. G., Haseltine W. A., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Essex M. Antigens encoded by the 3'-terminal region of human T-cell leukemia virus: evidence for a functional gene. Science. 1984 Oct 5;226(4670):57–61. doi: 10.1126/science.6089350. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Nagashima K., Yoshida M., Seiki M. A single species of pX mRNA of human T-cell leukemia virus type I encodes trans-activator p40x and two other phosphoproteins. J Virol. 1986 Nov;60(2):394–399. doi: 10.1128/jvi.60.2.394-399.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. 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]
  28. Preston C. M., Frame M. C., Campbell M. E. A complex formed between cell components and an HSV structural polypeptide binds to a viral immediate early gene regulatory DNA sequence. Cell. 1988 Feb 12;52(3):425–434. doi: 10.1016/s0092-8674(88)80035-7. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Rauscher F. J., 3rd, Sambucetti L. C., Curran T., Distel R. J., Spiegelman B. M. Common DNA binding site for Fos protein complexes and transcription factor AP-1. Cell. 1988 Feb 12;52(3):471–480. doi: 10.1016/s0092-8674(88)80039-4. [DOI] [PubMed] [Google Scholar]
  31. Reichel R., Kovesdi I., Nevins J. R. Activation of a preexisting cellular factor as a basis for adenovirus E1A-mediated transcription control. Proc Natl Acad Sci U S A. 1988 Jan;85(2):387–390. doi: 10.1073/pnas.85.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Sassone-Corsi P., Lamph W. W., Kamps M., Verma I. M. fos-associated cellular p39 is related to nuclear transcription factor AP-1. Cell. 1988 Aug 12;54(4):553–560. doi: 10.1016/0092-8674(88)90077-3. [DOI] [PubMed] [Google Scholar]
  34. Seiki M., Hikikoshi A., Taniguchi T., Yoshida M. Expression of the pX gene of HTLV-I: general splicing mechanism in the HTLV family. Science. 1985 Jun 28;228(4707):1532–1534. doi: 10.1126/science.2990031. [DOI] [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. Slamon D. J., Shimotohno K., Cline M. J., Golde D. W., Chen I. S. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science. 1984 Oct 5;226(4670):61–65. doi: 10.1126/science.6089351. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Takahashi K., Vigneron M., Matthes H., Wildeman A., Zenke M., Chambon P. Requirement of stereospecific alignments for initiation from the simian virus 40 early promoter. Nature. 1986 Jan 9;319(6049):121–126. doi: 10.1038/319121a0. [DOI] [PubMed] [Google Scholar]
  39. Wachsman W., Shimotohno K., Clark S. C., Golde D. W., Chen I. S. Expression of the 3' terminal region of human T-cell leukemia viruses. Science. 1984 Oct 12;226(4671):177–179. doi: 10.1126/science.6091270. [DOI] [PubMed] [Google Scholar]
  40. Whyte P., Buchkovich K. J., Horowitz J. M., Friend S. H., Raybuck M., Weinberg R. A., Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature. 1988 Jul 14;334(6178):124–129. doi: 10.1038/334124a0. [DOI] [PubMed] [Google Scholar]

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