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Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I

Abstract

The trans-activator protein Tax of human T-cell leukemia virus type I (HTLV-I) plays an important role in the development of adult T-cell leukemia through, at least in part, its ability to stimulate cell growth. We previously reported that Tax induced cell cycle progression from G0/G1 phase to S and G2/M phases in human T-cell line Kit 225 cells. To elucidate molecular mechanism of Tax-induced cell cycle progression, we systematically examined the effects of Tax on biochemical events associated with cell cycle progression. Introduction of Tax into resting Kit 225 cells induced activation of the G1/S transition regulation cascade consisting of activation of cyclin dependent kinase 2 (CDK2) and CDK4, phosphorylation of the Rb family proteins and an increase in free E2F. The kinase activation was found to result from Tax-induced expression of genes for cell cycle regulatory molecules including cyclin D2, cyclin E, E2F1, CDK2, CDK4 and CDK6, and Tax-induced reduction of CDK inhibitors p19INK4d and p27Kip1. These modulations by Tax always paralleled the ability of Tax to activate the NF-κB transcription pathway. These results indicate the important role of Tax-mediated trans-activation of the genes for cell cycle regulatory molecules in Tax-induced cell cycle progression.

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References

  • Akagi T, Ono H, Shimotohno K . 1995 Blood 86: 4243–4249

  • Akagi T, Ono H, Shimotohno K . 1996 Oncogene 12: 1645–1652

  • DeGregori J, Leone G, Ohtani K, Miron A, Nevins JR . 1995 Genes Dev. 9: 2873–2887

  • Dyson N . 1998 Genes Dev. 12: 2245–2262

  • Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J, Livingston DM . 1993 Cell 73: 487–497

  • Felber BK, Paskaris H, Kleinman-Ewing C, Wong-Staal F, Pavlakis GN . 1985 Science 229: 675–679

  • Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de The G . 1985 Lancet ii: 407–410

  • Ginsberg D, Vairo G, Chittenden T, Xiao ZX, Xu G, Wydner KL, DeCaprio JA, Lawrence JB, Livingston DM . 1994 Genes Dev. 8: 2665–2679

  • Graham FL, Smiley J, Russell WC, Nairn R . 1977 J. Gen. Virol. 36: 59–74

  • Grassmann R, Dengler C, Muller-Fleckenstein I, Fleckenstein B, McGuire K, Dokhelar MC, Sodroski JG, Haseltine WA . 1989 Proc. Natl. Acad. Sci. USA 86: 3351–3355

  • Grossman WJ, Kimata JT, Wong FH, Zutter M, Ley TJ, Ratner L . 1995 Proc. Natl. Acad. Sci. USA 92: 1057–1061

  • Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI, Weinberg RA . 1992 Cell 70: 993–1006

  • Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I . 1981 Proc. Natl. Acad. Sci. USA 78: 6476–6480

  • Hirai H, Fujisawa J, Suzuki T, Ueda K, Muramatsu M, Tsuboi A, Arai N, Yoshida M . 1992 Oncogene 7: 1737–1742

  • Hori T, Uchiyama T, Tsudo M, Umadome H, Ohno H, Fukuhara S, Kita K, Uchino H . 1987 Blood 70: 1069–1072

  • Hoshikawa Y, Mori A, Amimoto K, Iwabe K, Hatakeyama M . 1998 Proc. Natl. Acad. Sci. USA 95: 8574–8579

  • Ikeda MA, Jakoi L, Nevins JR . 1996 Proc. Natl. Acad. Sci. USA 93: 3215–3220

  • Iwanaga Y, Tsukahara T, Ohashi T, Tanaka Y, Arai M, Nakamura M, Ohtani K, Koya Y, Kannagi M, Yamamoto N, Fujii M . 1999 J. Virol. 73: 1271–1277

  • Johnson DG, Ohtani K, Nevins JR . 1994 Genes Dev. 8: 1514–1525

  • Johnson DG, Schwarz JK, Cress WD, Nevins JR . 1993 Nature 365: 349–352

  • LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E . 1997 Genes Dev. 11: 847–862

  • Lauper N, Beck AR, Cariou S, Richman L, Hofmann K, Reith W, Slingerland JM, Amati B . 1998 Oncogene 17: 2637–2643

  • Lee B, Tanaka Y, Tozawa H . 1989 Tohoku J. Exp. Med. 157: 1–11

  • Lees JA, Saito M, Vidal M, Valentine M, Look T, Harlow E, Dyson N, Helin K . 1993 Mol. Cell. Biol. 13: 7813–7825

  • Low KG, Dorner LF, Fernando DB, Grossman J, Jeang KT, Comb MJ . 1997 J. Virol. 71: 1956–1962

  • Minowada J, Onuma T, Moore GE . 1972 J. Natl. Cancer Inst. 49: 891–895

  • Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, Nagata K, Hinuma Y . 1981 Nature 294: 770–771

  • Nerenberg M, Hinrichs SH, Reynolds RK, Khoury G, Jay G . 1987 Science 237: 1324–1329

  • Nevins JR . 1992 Science 258: 424–429

  • Ohtani K, Iwanaga R, Arai M, Huang Y, Matsumura Y, Nakamura M . 2000 J. Biol. Chem. 275: 11154–11163

  • Osame M, Igata A, Usuku K, Rosales RL, Matsumoto M . 1986 Lancet i: 1031–1032

  • Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC . 1980 Proc. Natl. Acad. Sci. USA 77: 7415–7419

  • Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF, Sherr CJ . 1993 Genes Dev. 7: 1559–1571

  • Schwarz JK, Bassing CH, Kovesdi I, Datto MB, Blazing M, George S, Wang XF, Nevins JR . 1995 Proc. Natl. Acad. Sci. USA 92: 483–487

  • Seiki M, Hattori S, Hirayama Y, Yoshida M . 1986 EMBO J. 5: 561–565

  • Smith EJ, Leone G, DeGregori J, Jakoi L, Nevins JR . 1996 Mol. Cell. Biol. 16: 6965–6976

  • Sodroski J, Rosen C, Goh WC, Haseltine W . 1985 Science 228: 1430–1434

  • Suzuki T, Kitao S, Matsushime H, Yoshida M . 1996 EMBO J. 15: 1607–1614

  • Suzuki T, Narita T, Uchida-Toita M, Yoshida M . 1999 Virology 259: 384–391

  • Tanaka A, Takahashi C, Yamaoka S, Nosaka T, Maki M, Hatanaka M . 1990 Proc. Natl. Acad. Sci. USA 87: 1071–1075

  • van den Heuvel S, Harlow E . 1993 Science 262: 2050–2054

  • Yoshida M . 1995 J. Cancer Res. Clin. Oncol. 121: 521–528

  • Yoshida M, Miyoshi I, Hinuma Y . 1982 Proc. Natl. Acad. Sci. USA 79: 2031–2035

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Acknowledgements

We thank J Hamuro for IL-2, B Amati and G Peters for plasmids and M Yoshida for recombinant adenoviruses. This work was supported in part by a Grant-in-Aid for General Scientific Research and Cancer Research from the Ministry of Education, Science, Sports and Culture, in part by a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (JST), in part by a grant from NOVARTIS Foundation (Japan) for the Promotion of Science, in part by a grant from Osaka Cancer Foundation, and in part by a grant from The Naito Foundation.

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Iwanaga, R., Ohtani, K., Hayashi, T. et al. Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I. Oncogene 20, 2055–2067 (2001). https://doi.org/10.1038/sj.onc.1204304

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