Skip to main content
PMC home page
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
. 1992 Aug 1;89(15):7070–7074. doi: 10.1073/pnas.89.15.7070

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.

L J Zhao 1, C Z Giam 1
PMCID: PMC49647  PMID: 1386673

Abstract

HTLV-I Tax protein activates transcription from three 21-base-pair (bp) repeat sequences in the viral enhancer. The HTLV-I 21-bp repeat contains a TGACGT motif that is homologous to the cAMP-responsive element (CRE) and crucial for tax transactivation. Tax exhibits marginal affinity for DNA but rather interacts with cellular CRE-binding proteins to enhance their affinity for the HTLV-I 21-bp repeats. Using the HTLV-I 21-bp repeat and Jurkat T-lymphocyte nuclear extract in a gel electrophoretic mobility-shift assay, we previously detected three protein-DNA complexes that are specific for the CRE in the 21-bp repeat (complexes I, II, and IV). Complexes I and II but not IV interacted with Tax. We now show that complexes I, II, and IV are composed of CREB (CRE binding protein) homodimer, CREB/ATF-1 (activating transcription factor 1) heterodimer, and ATF-1 homodimer, respectively. Tax stabilizes complexes I and II via a direct interaction with the CREB moiety. In the absence of DNA, CREB and Tax continue to form a complex that can be immunoprecipitated by a Tax-specific antibody. These results suggest that one mechanism by which Tax activates transcription may be mediated through the direct interaction with CREB homodimer and/or CREB/ATF-1 heterodimer to stabilize their assembly on the Tax-responsive CRE motifs in the HTLV-I enhancer.

Full text

PDF
7070

Images in this article

7071Image
on p.7071
7071Image
on p.7071
7072Image
on p.7072
7073Image
on p.7073

Selected References

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

  1. 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]
  2. 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]
  3. 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]
  4. Giam C. Z., Nerenberg M., Khoury G., Jay G. Expression of the complete human T-cell leukemia virus type I pX coding sequence as a functional protein in Escherichia coli. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7192–7196. doi: 10.1073/pnas.83.19.7192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Giam C. Z., Xu Y. L. HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element. J Biol Chem. 1989 Sep 15;264(26):15236–15241. [PubMed] [Google Scholar]
  6. Gonzalez G. A., Yamamoto K. K., Fischer W. H., Karr D., Menzel P., Biggs W., 3rd, Vale W. W., Montminy M. R. A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence. Nature. 1989 Feb 23;337(6209):749–752. doi: 10.1038/337749a0. [DOI] [PubMed] [Google Scholar]
  7. Greenblatt J. Roles of TFIID in transcriptional initiation by RNA polymerase II. Cell. 1991 Sep 20;66(6):1067–1070. doi: 10.1016/0092-8674(91)90027-v. [DOI] [PubMed] [Google Scholar]
  8. Greene W. C., Böhnlein E., Ballard D. W. HIV-1, HTLV-1 and normal T-cell growth: transcriptional strategies and surprises. Immunol Today. 1989 Aug;10(8):272–278. doi: 10.1016/0167-5699(89)90141-2. [DOI] [PubMed] [Google Scholar]
  9. Habener J. F. Cyclic AMP response element binding proteins: a cornucopia of transcription factors. Mol Endocrinol. 1990 Aug;4(8):1087–1094. doi: 10.1210/mend-4-8-1087. [DOI] [PubMed] [Google Scholar]
  10. Hai T. W., Liu F., Coukos W. J., Green M. R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083–2090. doi: 10.1101/gad.3.12b.2083. [DOI] [PubMed] [Google Scholar]
  11. Hanly S. M., Rimsky L. T., Malim M. H., Kim J. H., Hauber J., Duc Dodon M., Le S. Y., Maizel J. V., Cullen B. R., Greene W. C. Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements. Genes Dev. 1989 Oct;3(10):1534–1544. doi: 10.1101/gad.3.10.1534. [DOI] [PubMed] [Google Scholar]
  12. Hardy S., Shenk T. Adenoviral control regions activated by E1A and the cAMP response element bind to the same factor. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4171–4175. doi: 10.1073/pnas.85.12.4171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoeffler J. P., Meyer T. E., Yun Y., Jameson J. L., Habener J. F. Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. Science. 1988 Dec 9;242(4884):1430–1433. doi: 10.1126/science.2974179. [DOI] [PubMed] [Google Scholar]
  14. Hurst H. C., Masson N., Jones N. C., Lee K. A. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43. Mol Cell Biol. 1990 Dec;10(12):6192–6203. doi: 10.1128/mcb.10.12.6192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hurst H. C., Totty N. F., Jones N. C. Identification and functional characterisation of the cellular activating transcription factor 43 (ATF-43) protein. Nucleic Acids Res. 1991 Sep 11;19(17):4601–4609. doi: 10.1093/nar/19.17.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kadison P., Poteat H. T., Klein K. M., Faller D. V. Role of protein kinase A in tax transactivation of the human T-cell leukemia virus type I long terminal repeat. J Virol. 1990 May;64(5):2141–2148. doi: 10.1128/jvi.64.5.2141-2148.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lin Y. S., Green M. R. Interaction of a common cellular transcription factor, ATF, with regulatory elements in both E1a- and cyclic AMP-inducible promoters. Proc Natl Acad Sci U S A. 1988 May;85(10):3396–3400. doi: 10.1073/pnas.85.10.3396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Poteat H. T., Chen F. Y., Kadison P., Sodroski J. G., Haseltine W. A. Protein kinase A-dependent binding of a nuclear factor to the 21-base-pair repeat of the human T-cell leukemia virus type I long terminal repeat. J Virol. 1990 Mar;64(3):1264–1270. doi: 10.1128/jvi.64.3.1264-1270.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Poteat H. T., Kadison P., McGuire K., Park L., Park R. E., Sodroski J. G., Haseltine W. A. Response of the human T-cell leukemia virus type 1 long terminal repeat to cyclic AMP. J Virol. 1989 Apr;63(4):1604–1611. doi: 10.1128/jvi.63.4.1604-1611.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roesler W. J., Vandenbark G. R., Hanson R. W. Cyclic AMP and the induction of eukaryotic gene transcription. J Biol Chem. 1988 Jul 5;263(19):9063–9066. [PubMed] [Google Scholar]
  24. Rosen C. A., Sodroski J. G., Haseltine W. A. Location of cis-acting regulatory sequences in the human T-cell leukemia virus type I long terminal repeat. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6502–6506. doi: 10.1073/pnas.82.19.6502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  27. Tan T. H., Jia R., Roeder R. G. Utilization of signal transduction pathway by the human T-cell leukemia virus type I transcriptional activator tax. J Virol. 1989 Sep;63(9):3761–3768. doi: 10.1128/jvi.63.9.3761-3768.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tsujimoto A., Nyunoya H., Morita T., Sato T., Shimotohno K. Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I. J Virol. 1991 Mar;65(3):1420–1426. doi: 10.1128/jvi.65.3.1420-1426.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Waeber G., Meyer T. E., LeSieur M., Hermann H. L., Gérard N., Habener J. F. Developmental stage-specific expression of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB during spermatogenesis involves alternative exon splicing. Mol Endocrinol. 1991 Oct;5(10):1418–1430. doi: 10.1210/mend-5-10-1418. [DOI] [PubMed] [Google Scholar]
  30. Wong-Staal F., Gallo R. C. Human T-lymphotropic retroviruses. Nature. 1985 Oct 3;317(6036):395–403. doi: 10.1038/317395a0. [DOI] [PubMed] [Google Scholar]
  31. Xu Y. L., Adya N., Siores E., Gao Q. S., Giam C. Z. Cellular factors involved in transcription and Tax-mediated trans-activation directed by the TGACGT motifs in human T-cell leukemia virus type I promoter. J Biol Chem. 1990 Nov 25;265(33):20285–20292. [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. 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 Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES