Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1994 Nov;68(11):7275–7283. doi: 10.1128/jvi.68.11.7275-7283.1994

Serum response factor has functional roles both in indirect binding to the CArG box and in the transcriptional activation function of human T-cell leukemia virus type I Tax.

M Fujii 1, H Tsuchiya 1, T Chuhjo 1, T Minamino 1, K Miyamoto 1, M Seiki 1
PMCID: PMC237168  PMID: 7933111

Abstract

We previously reported that Tax1 of human T-cell leukemia virus type I interacts directly with serum response factor (SRF) and that Tax1 activates the transcription of several cellular immediate-early genes through the SRF binding site (CArG box). This activation required the transcriptional activation function of Tax1, identified as an activity of GALTax (a chimeric Tax1 with the yeast transcription factor GAL4) at the GAL4-binding site. In this study, we examined whether SRF plays a role in the transcriptional activation function of Tax1. Expression of Tax1 suppressed the GALTax activity at the GAL4 site as a result of squelching, and the suppressed activity was recovered by the overexpression of SRF, suggesting that SRF is a factor that is required for GALTax activity and that is inhibited by competition with Tax1. The expression of antisense SRF RNA specifically inhibited GALTax activity to less than 20%. Deletion of the Tax1 interaction domain of SRF at its C terminus converted SRF from an activator of GALTax to an inhibitor. These results suggest that SRF is an essential component of the transcriptional activation of Tax1 in addition to a mediator of CArG box binding.

Full text

PDF
7283

Images in this article

7277Image
on p.7277
7277Image
on p.7277
7279Image
on p.7279
7280Image
on p.7280

Selected References

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

  1. Akagi T., Shimotohno K. Proliferative response of Tax1-transduced primary human T cells to anti-CD3 antibody stimulation by an interleukin-2-independent pathway. J Virol. 1993 Mar;67(3):1211–1217. doi: 10.1128/jvi.67.3.1211-1217.1993. [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. Caron C., Rousset R., Béraud C., Moncollin V., Egly J. M., Jalinot P. Functional and biochemical interaction of the HTLV-I Tax1 transactivator with TBP. EMBO J. 1993 Nov;12(11):4269–4278. doi: 10.1002/j.1460-2075.1993.tb06111.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Derse D. Bovine leukemia virus transcription is controlled by a virus-encoded trans-acting factor and by cis-acting response elements. J Virol. 1987 Aug;61(8):2462–2471. doi: 10.1128/jvi.61.8.2462-2471.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duyao M. P., Kessler D. J., Spicer D. B., Bartholomew C., Cleveland J. L., Siekevitz M., Sonenshein G. E. Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF kappa B. J Biol Chem. 1992 Aug 15;267(23):16288–16291. [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. Fujii M., Tsuchiya H., Seiki M. HTLV-1 Tax has distinct but overlapping domains for transcriptional activation and for enhancer specificity. Oncogene. 1991 Dec;6(12):2349–2352. [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. 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]
  18. Green P. L., Chen I. S. Regulation of human T cell leukemia virus expression. FASEB J. 1990 Feb 1;4(2):169–175. doi: 10.1096/fasebj.4.2.2404818. [DOI] [PubMed] [Google Scholar]
  19. Green S., Issemann I., Sheer E. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res. 1988 Jan 11;16(1):369–369. doi: 10.1093/nar/16.1.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Henkel T., Zabel U., van Zee K., Müller J. M., Fanning E., Baeuerle P. A. Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-kappa B subunit. Cell. 1992 Mar 20;68(6):1121–1133. doi: 10.1016/0092-8674(92)90083-o. [DOI] [PubMed] [Google Scholar]
  22. Hill C. S., Marais R., John S., Wynne J., Dalton S., Treisman R. Functional analysis of a growth factor-responsive transcription factor complex. Cell. 1993 Apr 23;73(2):395–406. doi: 10.1016/0092-8674(93)90238-l. [DOI] [PubMed] [Google Scholar]
  23. Hirai H., Fujisawa J., Suzuki T., Ueda K., Muramatsu M., Tsuboi A., Arai N., Yoshida M. Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105. Oncogene. 1992 Sep;7(9):1737–1742. [PubMed] [Google Scholar]
  24. Horikoshi N., Maguire K., Kralli A., Maldonado E., Reinberg D., Weinmann R. Direct interaction between adenovirus E1A protein and the TATA box binding transcription factor IID. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5124–5128. doi: 10.1073/pnas.88.12.5124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Johansen F. E., Prywes R. Identification of transcriptional activation and inhibitory domains in serum response factor (SRF) by using GAL4-SRF constructs. Mol Cell Biol. 1993 Aug;13(8):4640–4647. doi: 10.1128/mcb.13.8.4640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Katoh I., Yoshinaka Y., Ikawa Y. Bovine leukemia virus trans-activator p38tax activates heterologous promoters with a common sequence known as a cAMP-responsive element or the binding site of a cellular transcription factor ATF. EMBO J. 1989 Feb;8(2):497–503. doi: 10.1002/j.1460-2075.1989.tb03403.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kolodziej P. A., Young R. A. Epitope tagging and protein surveillance. Methods Enzymol. 1991;194:508–519. doi: 10.1016/0076-6879(91)94038-e. [DOI] [PubMed] [Google Scholar]
  30. Lee W. S., Kao C. C., Bryant G. O., Liu X., Berk A. J. Adenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell. 1991 Oct 18;67(2):365–376. doi: 10.1016/0092-8674(91)90188-5. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Lillie J. W., Green M. R. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. doi: 10.1038/338039a0. [DOI] [PubMed] [Google Scholar]
  33. Lin Y. S., Green M. R. Mechanism of action of an acidic transcriptional activator in vitro. Cell. 1991 Mar 8;64(5):971–981. doi: 10.1016/0092-8674(91)90321-o. [DOI] [PubMed] [Google Scholar]
  34. Liu F., Green M. R. A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein. Cell. 1990 Jun 29;61(7):1217–1224. doi: 10.1016/0092-8674(90)90686-9. [DOI] [PubMed] [Google Scholar]
  35. Martin K. J., Lillie J. W., Green M. R. Evidence for interaction of different eukaryotic transcriptional activators with distinct cellular targets. Nature. 1990 Jul 12;346(6280):147–152. doi: 10.1038/346147a0. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. 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]
  39. Norman C., Runswick M., Pollock R., Treisman R. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell. 1988 Dec 23;55(6):989–1003. doi: 10.1016/0092-8674(88)90244-9. [DOI] [PubMed] [Google Scholar]
  40. Pozzatti R., Vogel J., Jay G. The human T-lymphotropic virus type I tax gene can cooperate with the ras oncogene to induce neoplastic transformation of cells. Mol Cell Biol. 1990 Jan;10(1):413–417. doi: 10.1128/mcb.10.1.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Sadowski I., Ma J., Triezenberg S., Ptashne M. GAL4-VP16 is an unusually potent transcriptional activator. Nature. 1988 Oct 6;335(6190):563–564. doi: 10.1038/335563a0. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. 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]
  45. 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]
  46. Stern S., Tanaka M., Herr W. The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16. Nature. 1989 Oct 19;341(6243):624–630. doi: 10.1038/341624a0. [DOI] [PubMed] [Google Scholar]
  47. Stringer K. F., Ingles C. J., Greenblatt J. Direct and selective binding of an acidic transcriptional activation domain to the TATA-box factor TFIID. Nature. 1990 Jun 28;345(6278):783–786. doi: 10.1038/345783a0. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. Triezenberg S. J., Kingsbury R. C., McKnight S. L. Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression. Genes Dev. 1988 Jun;2(6):718–729. doi: 10.1101/gad.2.6.718. [DOI] [PubMed] [Google Scholar]
  51. Tsuchiya H., Fujii M., Niki T., Tokuhara M., Matsui M., Seiki M. Human T-cell leukemia virus type 1 Tax activates transcription of the human fra-1 gene through multiple cis elements responsive to transmembrane signals. J Virol. 1993 Dec;67(12):7001–7007. doi: 10.1128/jvi.67.12.7001-7007.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Tsuchiya H., Fujii M., Tanaka Y., Tozawa H., Seiki M. Two distinct regions form a functional activation domain of the HTLV-1 trans-activator Tax1. Oncogene. 1994 Jan;9(1):337–340. [PubMed] [Google Scholar]
  53. Uchijima M., Sato H., Fujii M., Seiki M. Tax proteins of human T-cell leukemia virus type 1 and 2 induce expression of the gene encoding erythroid-potentiating activity (tissue inhibitor of metalloproteinases-1, TIMP-1). J Biol Chem. 1994 May 27;269(21):14946–14950. [PubMed] [Google Scholar]
  54. Willems L., Chen G., Portetelle D., Mamoun R., Burny A., Kettmann R. Structural and functional characterization of mutants of the bovine leukemia virus transactivator protein p34. Virology. 1989 Aug;171(2):615–618. doi: 10.1016/0042-6822(89)90633-8. [DOI] [PubMed] [Google Scholar]
  55. Willems L., Kettmann R., Burny A. The amino acid (157-197) peptide segment of bovine leukemia virus p34tax encompass a leucine-rich globally neutral activation domain. Oncogene. 1991 Jan;6(1):159–163. [PubMed] [Google Scholar]
  56. Yoshida M., Inoue J., Fujisawa J., Seiki M. Molecular mechanisms of regulation of HTLV-1 gene expression and its association with leukemogenesis. Genome. 1989;31(2):662–667. doi: 10.1139/g89-121. [DOI] [PubMed] [Google Scholar]
  57. 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]

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

RESOURCES