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. 1994 May;68(5):3374–3379. doi: 10.1128/jvi.68.5.3374-3379.1994

The human T-cell leukemia virus type I Tax protein induces apoptosis which is blocked by the Bcl-2 protein.

T Yamada 1, S Yamaoka 1, T Goto 1, M Nakai 1, Y Tsujimoto 1, M Hatanaka 1
PMCID: PMC236829  PMID: 8151796

Abstract

The Tax protein of human T-cell leukemia virus type I activates transcription of cellular and viral genes and can immortalize primary T lymphocytes. We have previously reported that the Tax protein transforms Rat-1 cells. Here we show that Tax-transformed Rat-1 cells detach from plates to undergo apoptotic cell death by serum deprivation. These cells exhibit DNA fragmentation into oligonucleosomal fragments and chromatin condensation. Constitutive expression of a proto-oncogene, bcl-2, effectively blocks Tax-mediated apoptosis caused by serum deprivation without affecting the levels of Tax expression and the transformed phenotype of the cells.

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Selected References

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  1. 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]
  2. Armstrong A. P., Franklin A. A., Uittenbogaard M. N., Giebler H. A., Nyborg J. K. Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7303–7307. doi: 10.1073/pnas.90.15.7303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Askew D. S., Ashmun R. A., Simmons B. C., Cleveland J. L. Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene. 1991 Oct;6(10):1915–1922. [PubMed] [Google Scholar]
  4. Clarke A. R., Purdie C. A., Harrison D. J., Morris R. G., Bird C. C., Hooper M. L., Wyllie A. H. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature. 1993 Apr 29;362(6423):849–852. doi: 10.1038/362849a0. [DOI] [PubMed] [Google Scholar]
  5. Colotta F., Polentarutti N., Sironi M., Mantovani A. Expression and involvement of c-fos and c-jun protooncogenes in programmed cell death induced by growth factor deprivation in lymphoid cell lines. J Biol Chem. 1992 Sep 15;267(26):18278–18283. [PubMed] [Google Scholar]
  6. 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]
  7. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  8. Henderson S., Rowe M., Gregory C., Croom-Carter D., Wang F., Longnecker R., Kieff E., Rickinson A. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 1991 Jun 28;65(7):1107–1115. doi: 10.1016/0092-8674(91)90007-l. [DOI] [PubMed] [Google Scholar]
  9. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Izumi M., Miyazawa H., Kamakura T., Yamaguchi I., Endo T., Hanaoka F. Blasticidin S-resistance gene (bsr): a novel selectable marker for mammalian cells. Exp Cell Res. 1991 Dec;197(2):229–233. doi: 10.1016/0014-4827(91)90427-v. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Korsmeyer S. J. Bcl-2: an antidote to programmed cell death. Cancer Surv. 1992;15:105–118. [PubMed] [Google Scholar]
  14. Leung S., Miyamoto N. G. Point mutational analysis of the human c-fos serum response factor binding site. Nucleic Acids Res. 1989 Feb 11;17(3):1177–1195. doi: 10.1093/nar/17.3.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lowe S. W., Ruley H. E. Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev. 1993 Apr;7(4):535–545. doi: 10.1101/gad.7.4.535. [DOI] [PubMed] [Google Scholar]
  16. Lowe S. W., Schmitt E. M., Smith S. W., Osborne B. A., Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993 Apr 29;362(6423):847–849. doi: 10.1038/362847a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Rao L., Debbas M., Sabbatini P., Hockenbery D., Korsmeyer S., White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742–7746. doi: 10.1073/pnas.89.16.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sakurai M., Yamaoka S., Nosaka T., Akayama M., Tanaka A., Maki M., Hatanaka M. Transforming activity and the level of Tax protein: effect of one point mutation in HTLV-I tax gene. Int J Cancer. 1992 Sep 9;52(2):323–328. doi: 10.1002/ijc.2910520228. [DOI] [PubMed] [Google Scholar]
  21. Shi Y., Glynn J. M., Guilbert L. J., Cotter T. G., Bissonnette R. P., Green D. R. Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science. 1992 Jul 10;257(5067):212–214. doi: 10.1126/science.1378649. [DOI] [PubMed] [Google Scholar]
  22. Smeyne R. J., Vendrell M., Hayward M., Baker S. J., Miao G. G., Schilling K., Robertson L. M., Curran T., Morgan J. I. Continuous c-fos expression precedes programmed cell death in vivo. Nature. 1993 May 13;363(6425):166–169. doi: 10.1038/363166a0. [DOI] [PubMed] [Google Scholar]
  23. Smith M. R., Greene W. C. Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes. Genes Dev. 1990 Nov;4(11):1875–1885. doi: 10.1101/gad.4.11.1875. [DOI] [PubMed] [Google Scholar]
  24. Smith M. R., Greene W. C. Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. J Clin Invest. 1991 Sep;88(3):1038–1042. doi: 10.1172/JCI115364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Tsuda H., Huang R. W., Takatsuki K. Interleukin-2 prevents programmed cell death in adult T-cell leukemia cells. Jpn J Cancer Res. 1993 Apr;84(4):431–437. doi: 10.1111/j.1349-7006.1993.tb00154.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tsujimoto Y. Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1958–1962. doi: 10.1073/pnas.86.6.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wagner A. J., Small M. B., Hay N. Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. Mol Cell Biol. 1993 Apr;13(4):2432–2440. doi: 10.1128/mcb.13.4.2432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wang Y., Ramqvist T., Szekely L., Axelson H., Klein G., Wiman K. G. Reconstitution of wild-type p53 expression triggers apoptosis in a p53-negative v-myc retrovirus-induced T-cell lymphoma line. Cell Growth Differ. 1993 Jun;4(6):467–473. [PubMed] [Google Scholar]
  30. Weiss R. A., Schulz T. F. Transforming properties of the HTLV-I tax gene. Cancer Cells. 1990 Aug-Sep;2(8-9):281–283. [PubMed] [Google Scholar]
  31. White E., Cipriani R., Sabbatini P., Denton A. Adenovirus E1B 19-kilodalton protein overcomes the cytotoxicity of E1A proteins. J Virol. 1991 Jun;65(6):2968–2978. doi: 10.1128/jvi.65.6.2968-2978.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Whyte P., Ruley H. E., Harlow E. Two regions of the adenovirus early region 1A proteins are required for transformation. J Virol. 1988 Jan;62(1):257–265. doi: 10.1128/jvi.62.1.257-265.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Williams G. T., Smith C. A. Molecular regulation of apoptosis: genetic controls on cell death. Cell. 1993 Sep 10;74(5):777–779. doi: 10.1016/0092-8674(93)90457-2. [DOI] [PubMed] [Google Scholar]
  34. Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]
  35. Yonish-Rouach E., Resnitzky D., Lotem J., Sachs L., Kimchi A., Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 1991 Jul 25;352(6333):345–347. doi: 10.1038/352345a0. [DOI] [PubMed] [Google Scholar]

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