Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Genomic instability driven by the human T-cell leukemia virus type I (HTLV-I) oncoprotein, Tax

Oncogene volume 21, pages 7230–7234 (2002)Cite this article

Abstract

The importance of maintaining genomic stability is evidenced by the fact that transformed cells often contain a variety of chromosomal abnormalities such as euploidy, translocations, and inversions. Gene amplification is a well-characterized hallmark of genomic instability thought to result from recombination events following the formation of double-strand, chromosomal breaks. Therefore, gene amplification frequency serves as an indicator of genomic stability. The PALA assay is designed to measure directly the frequency with which a specific gene, CAD, is amplified within a cell's genome. We have used the PALA assay to analyse the effects of the human T-cell leukemia virus type I (HTLV-I) oncoprotein, Tax, on genomic amplification. We demonstrate that Tax-expressing cells are five-times more likely to undergo gene amplification than control cells. Additionally, we show that Tax alters the ability of cells to undergo the typical PALA-mediated G1 phase cell cycle arrest, thereby allowing cells to replicate DNA in the absence of appropriate nucleotide pools. This effect is likely the mechanism by which Tax induces gene amplification. These data suggest that HTLV-I Tax alters the genomic stability of cells, an effect that may play an important role in Tax-mediated, HTLV-I associated cellular transformation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Akagi T, Ono H, Tsuchida N, Shimotohno K . 1997 FEBS Lett. 406: 263–266

  • Ariumi Y, Yamaoka S, Lin JY, Hirota M, Masui O, Taya Y, Shomotohno K . 2000 Oncogene 19: 1491–1499

  • Benner SE, Wahl GM, Von Hoff DD . 1991 Anticancer Drugs 2: 11–25

  • Cereseto A, Diella F, Mulloy JC, Cara A, Michieli P, Grassmann R, Franchini G, Klotman ME . 1996 Blood 88: 1551–1560

  • Chernova OB, Chernov MV, Agarwal ML, Taylor WR, Stark GR . 1995 Trends Biochem. Sci. 20: 431–434

  • Collins KD, Stark GR . 1971 J. Biol. Chem. 246: 6599–6605

  • Coquelle A, Pipiras E, Toledo F, Buttin G, Debatisse M . 1997 Cell 89: 215–225

  • Di Leonardo A, Linke SP, Clarkin K, Wahl GM . 1994 Genes Dev. 8: 2540–2551

  • Gartenhaus RB, Wang P . 1995 Leukemia 9: 2082–2086

  • Kao S-Y, Lemoine FJ, Marriott SJ . 2000a Oncogene 19: 2240–2248

  • Kao S-Y, Lemoine FJ, Marriott SJ . 2000b Res. Adv. in Virol. 1: 1–12

  • Kao S-Y, Marriott SJ . 1999 J. Virol. 73: 4299–4304

  • Kempe TD, Swyryd EA, Bruist M, Stark GR . 1976 Cell 9: 541–550

  • Kuo MT, Vyas RC, Jiang LX, Hittelman WN . 1994 Mol. Cell. Biol. 14: 5202–5211

  • Lemoine FJ, Marriott SJ . 2001 J. Biol. Chem. 276: 31851–31857

  • Lengauer C, Kinzler KW, Vogelstein B . 1998 Nature 396: 643–649

  • Linke SP, Clarkin KC, Di Leonardo A, Tsou A, Wahl GM . 1996 Genes Dev. 10: 934–947

  • Miyake H, Suzuki T, Hirai H, Yoshida M . 1999 Virology 253: 155–161

  • Mondello C, Riboni R, Rady M, Giulotto E, Nuzzo F . 1995 Mutat. Res. 346: 61–67

  • Mulloy JC, Kislyakova T, Cereseto A, Casareto L, LoMonico A, Fullen J, Lorenzi MV, Cara A, Nicot C, Giam CZ, Franchini G . 1998 J. Virol. 72: 8852–8860

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

  • Otto E, McCord S, Tlsty TD . 1989 J. Biol. Chem. 264: 3390–3396

  • Philpott SM, Buehring GC . 1999 J. Natl. Cancer Inst. 91: 933–942

  • Pise-Masison CA, Choi KS, Radonovich M, Dittmer J, Kim SJ, Brady JN . 1998a J. Virol. 72: 1165–1170

  • Pise-Masison CA, Radonovich M, Sakaguchi K, Appella E, Brady JN . 1998b J. Virol. 72: 6348–6355

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

  • Poupon MF, Smith KA, Chernova OB, Gilbert C, Stark GR . 1996 Mol. Biol. Cell 7: 345–354

  • Pozzatti R, Vogel J, Jay G . 1990 Mol. Cell. Biol. 10: 413–417

  • Reid RL, Lindholm PF, Mireskandari A, Dittmer J, Brady JN . 1993 Oncogene 8: 3029–3036

  • Smith KA, Agarwal ML, Chernov MV, Chernova OB, Deguchi Y, Ishizaka Y, Patterson TE, Poupon MF, Stark GR . 1995 Philos. Trans. R. Soc. Lond. B. Biol. Sci. 347: 49–56

  • Swyryd EA, Seaver SS, Stark GR . 1974 J. Biol. Chem. 249: 6945–6950

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

  • Tlsty TD . 1997 Curr. Top. Microbiol. Immunol. 221: 37–46

  • Wahl GM, Padgett RA, Stark GR . 1979 J. Biol. Chem. 254: 8679–8689

  • Wettergren Y, Kullberg A, Levan G . 1994 Somat. Cell. Mol. Genet. 20: 267–285

  • Windle B, Draper BW, Yin YX, O'Gorman S, Wahl GM . 1991 Genes Dev. 5: 160–174

  • Windle BE, Wahl GM . 1992 Mutat. Res. 276: 199–224

  • Wright JA, Smith HS, Watt FM, Hancock MC, Hudson DL, Stark GR . 1990 Proc. Natl. Acad. Sci. USA 87: 1791–1795

  • Yamaoka S, Tobe T, Hatanaka M . 1992 Oncogene 7: 433–437

Download references

Acknowledgements

We thank Drs Ronald Javier and Robert Weiss for providing CREF-neo and CREF-Tax cells, and Dr Stuart Tyner for help with Southern blots. We gratefully acknowledge the members of the Marriott laboratory for their helpful suggestions and comments. This study was supported in part by the United States Public Health Service Grant CA-77371 from National Cancer Institute, awarded to SJ Marriott. FJ Lemoine was supported by part by National Institutes of Health Training Grant CA-09197.

Author information

Authors and Affiliations

  1. Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Francene J Lemoine & Susan J Marriott

  2. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Susan J Marriott

Authors
  1. Francene J Lemoine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan J Marriott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan J Marriott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lemoine, F., Marriott, S. Genomic instability driven by the human T-cell leukemia virus type I (HTLV-I) oncoprotein, Tax. Oncogene 21, 7230–7234 (2002). https://doi.org/10.1038/sj.onc.1205898

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205898

Keywords

This article is cited by

Search

Advanced search

Quick links