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:

Inhibition of SV40 large T antigen induced apoptosis by small T antigen

Oncogene volume 18, pages 5598–5603 (1999)Cite this article

Abstract

It is well established that the expression of simian virus 40 (SV40) early gene products causes oncogenic transformation of rodent cells. An important aspect of this process is the inactivation of the p53 and retinoblastoma (pRb) tumour suppressor proteins through interaction with the SV40 large tumour antigen (LT). In addition, the SV40 small tumour antigen (ST) may enhance LT induced transformation. Here we show that LT induces apoptotic cell death in rat embryo fibroblast (REF) cells and that ST functions to inhibit this effect by a mechanism which is different from other known anti-apoptotic proteins. Mutational analysis of LT indicates that mutants defective in the pRb-binding domain are unable to induce apoptosis whereas LT mutants defective in the p53-binding domain are still competent to induce apoptosis. Thus, interaction between LT and one or more pRb family members must occur for induction of apoptosis and that binding of p53 by LT is insufficient to inhibit LT induced apoptosis in REFs. The data presented herein suggest that the anti-apoptotic function of ST may explain, at least in part, how ST contributes to SV40 early region induced transformation of REF cells.

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 3
Figure 2
Figure 4

Similar content being viewed by others

References

  • Al-Ubaidi MR, Mangini NJ, Quiambao AB, Myers KM, Abler AS, Chang CJ, Tso MO, Butel JS and Hollyfield JG. . 1997 Exp. Eye Res. 64: 573–585.

  • Bellett AJD and Younghusband HB. . 1979 J. Cell Physiol. 101: 33–48.

  • Bikel I, Mamon H, Brown L, Boltax J, Agha M and Livingston DM. . 1986 Mol. Cell Biol. 6: 1172–1178.

  • Bouck N, Beales N, Shenk T, Berg P and Di Mayorca G. . 1978 Proc. Natl. Acad. Sci. USA 75: 2473–2477.

  • Braithwaite AW, Sturzbecher HW, Addison C, Palmer C, Rudge K and Jenkins J. . 1987 Nature 329: 458–460.

  • Brown M, McCormack M, Zinn KG, Farrell MP, Bikel I and Livingston D. . 1986 J. Virol. 60: 290–293.

  • Chen SL, Tsao YP, Chen YL, Huang SJ, Chang JL and Wu SF. . 1998 Virology 244: 521–529.

  • Debbas M and White E. . 1993 Genes Dev. 7: 546–554.

  • Endo T and Nadal-Ginard B. . 1998 J. Cell Sci. 111: 1081–1093.

  • Fanning E. . 1992 J. Virol. 66: 1289–1293.

  • Fromm L, Shawlot W, Gunning K, Butel JS and Overbeek PA. . 1994 Mol. Cell Biol. 14: 6743–6754.

  • Fu XY and Manley JL. . 1987 Mol. Cell Biol. 7: 738–748.

  • Hansen RS. . 1995 PhD thesis Australian National University.

    Google Scholar 

  • Hansen RS and Braithwaite AW. . 1996 Oncogene 13: 995–1007.

  • Hansen RS, Reddel RR and Braithwaite AW. . 1995 Oncogene 11: 2535–2545.

  • Jat PS, Cepko CL, Mulligan RC and Sharp PA. . 1986 Mol. Cell Biol. 6: 1204–1217.

  • Jog P, Joshi B, Dhamankar V, Imperiale MJ, Rutila J and Rundell K. . 1990 J. Virol. 64: 5649–5651.

  • Kriegler M, Perez CF, Hardy C and Botchan M. . 1984 Cell 38: 483–491.

  • Li R, Suthpin PD, Schwartz D, Matas D, Almog D, Wolkowicz R, Goldfinger N, Pei H, Prokocimer M and Rotter V. . 1998 Oncogene 16: 3269–3277.

  • Lill NL, Tevethia MJ, Eckner R, Livingston DM and Modjtahedi N. . 1997 J. Virol. 71: 129–137.

  • Lin J-Y and Simmons DT. . 1991 J. Virol. 65: 6447–6453.

  • Maclean K, Rogan EM, Whitaker NJ, Chang ACM, Rowe PB, Dalla-Pozza L, Symonds G and Reddel RR. . 1994 Oncogene 9: 719–725.

  • Manfredi JJ and Prives C. . 1994 Biochim. Biophys. Acta Rev. 1198: 65–83.

  • Marcellus RC, Teodoro JG, Wu T, Brough DE, Ketner G, Shore GC and Branton PE. . 1996 J. Virol. 70: 6201–6215.

  • Montano X, Millikan R, Milhaven JM, Newsome DA, Ludlow JW, Arthur AK, Fanning E, Bikel I and Livingston DM. . 1990 Proc. Natl. Acad. Sci. USA 87: 7448–7452.

  • Naik P, Karrim J and Hanahan D. . 1996 Genes Dev. 10: 2105–2116.

  • Pallas DC, Shahrik LK, Martin L, Jaspers S, Miller TB, Brautigan LB and Roberts TM. . 1990 Cell 60: 167–176.

  • Paucha E, Mellor A, Harvey R, Smith AE, Hewick RM and Waterfield MD. . 1978 Proc. Natl. Acad. Sci. USA 75: 2165–2169.

  • Reed M, Wang Y, May RJ, Anderson ME, Schwedes JF and Tegtmeyer P. . 1993 Gene Expression 3: 95–107.

  • Sakamoto K, Howard T, Ogryzko V, Xu NZ, Corsico CC, Jones DH and Howard B. . 1993 Oncogene 8: 1887–1893.

  • Scheidtmann KH, Mumby MC, Rundell K and Walter G. . 1991 Mol. Cell Biol. 11: 1996–2003.

  • Sompayrac L and Danna KJ. . 1989 Virology 171: 267–270.

  • Sompayrac L and Danna KJ. . 1992 Virology 191: 439–442.

  • Southern PJ and Berg P. . 1982 J. Mol. Appl. Genetics 1: 327–341.

  • Srinivasan A, McClellan AJ, Vartikar J, Marks I, Cantalupo P, Li Y, Whyte P, Rundell K, Symonds H, Krall L, Remington L, Saenz-Robles M, Lowe S, Jacks T and van Dyke T. . 1994 Cell 78: 703–711.

  • Tiemann F, Zerrahn J and Deppert W. . 1995 J. Virol. 69: 6115–6121.

  • Watanabe G, Howe A, Lee RJ, Albanese C, Shu I-W, Karnezis AN, Zon L, Kyriakis J, Rundell K and Pestell RG. . 1996 Proc. Natl. Acad. Sci. USA 93: 12861–12866.

  • Yanai N and Obinata M. . 1994 Exp. Cell Res. 211: 296–300.

  • Yang SI, Lickteig RL, Estes R, Rundell K, Walter G and Mumby MC. . 1991 Mol. Cell Biol. 11: 1988–1995.

  • Zahra DG. . 1995 PhD. Thesis, University of Sydney.

    Google Scholar 

  • Zerrahn J, Knippschild U, Winkler T and Deppert W. . 1993 EMBO J. 12: 4739–4746.

Download references

Acknowledgements

We thank Dr M Reed (Stonybrook) for the p53ct expression plasmid, Dr D Simmons (Delaware) for the DE402 base construct, Dr L Sompayrac (Boulder) for the base constructs for mutants LE107 and aa147n. We also thank John Zhang for assistance with plasmid construction. This work was supported by grants from the Health Research Council of New Zealand, the Cancer Society of New Zealand and the Otago University Faculty Funds to A Braithwaite, and the Cancer Council of New South Wales to R Reddel.

Author information

Author notes

  1. R S Hansen

    Present address: Human Reproduction Journals, Cambridge, UK

  2. D Zahra

    Present address: The Garvan Institute, Sydney, Australia

  3. T Kolzau

    Present address: Eppendorf, Hamburg, Germany

Authors and Affiliations

  1. Department of Pathology, Dunedin School of Medicine, University of Otago, Box 913, Dunedin, New Zealand

    T Kolzau & A W Braithwaite

  2. Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, NSW 2145, Sydney, Australia

    D Zahra & R R Reddel

Authors
  1. T Kolzau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R S Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Zahra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R R Reddel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A W Braithwaite
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kolzau, T., Hansen, R., Zahra, D. et al. Inhibition of SV40 large T antigen induced apoptosis by small T antigen. Oncogene 18, 5598–5603 (1999). https://doi.org/10.1038/sj.onc.1202942

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202942

Keywords

This article is cited by

Search

Advanced search

Quick links