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.

  • Original Paper
  • Published:

Polyomavirus large T-antigen protects mouse cells from Fas-, TNF-α- and taxol-induced apoptosis

Oncogene volume 19, pages 6261–6270 (2000)Cite this article

Abstract

Polyomavirus large T-antigen (PyLT-Ag), a nucleophosphoprotein essential for regulating viral gene expression, modulates the cell cycle by binding to the Rb tumor suppressor gene product. PyLT-Ag/Rb binding is essential for in vitro immortalization. However, the effect of PyLT-Ag on apoptosis has not been extensively studied. We have previously reported that FasR agonist antibodies (FasR(Ab)) treatment of Sertoli cells derived from transgenic mice expressing PyLT-Ag induces the growth arrest of these cells without concomitant apoptosis. Here we show that stable expression of PyLT-Ag in murine Sertoli TM4 and hybridoma NSO cell lines confers protection from FasR(Ab)-induced apoptosis. The protection was maintained up to 48 h when cells were grown continuously in the presence of FasR(Ab). Removal of the death stimulus after 24 h exposure was sufficient to allow full recovery of the PyLT-Ag expressing cells. The protective effect conferred by PyLT-Ag was associated with a delay in the sequential activation of caspase-8 and -3 after FasR(Ab) treatment. PyLT-Ag co-precipitated following immunoprecipitation of caspase-8 or FADD, both components of the DISC. Based on these results we suggest that PyLT-Ag directly impedes the recruitment or activation of caspase-8 by the FasR. PyLT-Ag expression in TM4 cells was also associated with protection from TNF-α- and taxol-induced apoptosis. In contrast, PyLT-Ag expression was not sufficient to confer protection from captothecin-induced apoptosis. Taken together, these results indicate that PyLT-Ag can be a potent inhibitor of Fas(R)(Ab)-, TNF-α- and taxol-induced apoptosis.

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
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Alnemri ES. . 1997 J. Cell. Biochem. 64: 33–42.

  • Arrigo AP. . 1998 Biol. Chem. 379: 19–26.

  • Baker SJ and Reddy EP. . 1998 Oncogene 17: 3261–3270.

  • Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM and Green DR. . 2000 Nat. Cell. Biol. 2: 469–475.

  • Bertrand R, Kohn KW, Solary E and Pommier Y. . 1995 Drug Dev. Res. 34: 138–144.

  • Boldin MP, Goncharov TM, Goltsev YV and Wallach D. . 1996 Cell 85: 803–815.

  • Boyd JM, Malstrom S, Subramanian T, Venkatesh LK, Schaeper U, Elangovan B, D'Sa-Eipper C and Chinnadurai G. . 1994 Cell 79: 341–351.

  • Brodsky JL and Pipas JM. . 1998 J. Virol. 72: 5329–5334.

  • Chen G, Branton PE, Yang E, Korsmeyer SJ and Shore GC. . 1996 J. Biol. Chem. 271: 24221–24225.

  • Chinnaiyan AM and Dixit VM. . 1997 Semin. Immunol. 9: 69–76.

  • Chiou SK, Tseng CC, Rao L and White E. . 1994 J. Virol. 68: 6553–6566.

  • Conzen SD, Snay CA and Cole CN. . 1997 J. Virol. 71: 4536–4543.

  • Cryns V and Yuan JY. . 1998 Genes Dev. 12: 1551–1570.

  • Decaudin D, Marzo I, Brenner C and Kroemer G. . 1998 Intl. J. Oncol. 12: 141–152.

  • Dole MG, Jasty R, Cooper MJ, Thompson CB, Nunez G and Castle VP. . 1995 Cancer Res. 55: 2576–2582.

  • Earnshaw WC. . 1995 Curr. Opin. Cell Biol. 7: 337–343.

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

  • Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Tapani JA, Tomaselli KJ, Litwack G and Alnemri ES. . 1996 Proc. Natl. Acad. Sci. USA 93: 7464–7469.

  • Fimia GM, Gottifredi V, Bellei B, Ricciardi MR, Tafuri A, Amati P and Maione R. . 1998 Mol. Biol. Cell 9: 1449–1463.

  • Gonin S, Diaz-Latoud C, Richard MJ, Ursini MV, Imbo A, Manero F and Arrigo AP. . 1999 Oncogene 18: 8011–8023.

  • Gottifredi V, Peschiaroli A, Fimia GM and Maione R. . 1999 J. Cell Sci. 112: 2397–2407.

  • Han J, Sabbatini P and White E. . 1996 Mol. Cell Biol. 16: 5857–5864.

  • Han J, Wallen HD, Nunez G and White E. . 1998 Mol. Cell Biol. 18: 6052–6062.

  • Hirsch T, Marchetti P, Susin SA, Dallaporta B, Zamzami N, Marzo I, Geuskens M and Kroemer G. . 1997 Oncogene 15: 1573–1581.

  • Hohfeld J. . 1998 Biol. Chem. 379: 269–274.

  • Ibrado AM, Huang Y, Fang GF and Bhalla K. . 1996 Cell Growth Diff. 7: 1087–1094.

  • Imai Y, Kimura T, Murakami A, Yajima N, Sakamaki K and Yonehara S. . 1999 Nature 398: 777–785.

  • Jaattela M, Wissing D, Kokholm K, Kallunki T and Egeblad M. . 1998 EMBO J. 17: 6124–6134.

  • Jung YK and Yuan J. . 1997 Oncogene 14: 1207–1214.

  • Kelley WL and Georgopoulos C. . 1997 Proc. Natl. Acad. Sci. USA 94: 3679–3684.

  • Khandjian EW and Tremblay S. . 1992 Oncogene 7: 909–917.

  • Kharbanda S, Pandey P, Schofield L, Israels S, Roncinske R, Yoshida K, Bharti A, Yuan ZM, Saxena S, Weichselbaum R, Nalin C and Kufe D. . 1997 Proc. Natl. Acad. Sci. USA 94: 6939–6942.

  • Kidd VJ. . 1998 Annu. Rev. Physiol. 60: 533–573.

  • Kingston RE, Cowie A, Morimoto RI and Gwinn KA. . 1986 Mol. Cell Biol. 6: 3180–3190.

  • Larose A, Dyson N, Sullivan M, Harlow E and Bastin M. . 1991 J. Virol. 65: 2308–2313.

  • Larose A, St-Onge L and Bastin M. . 1990 Virology 176: 98–105.

  • Lazebnik YA, Takahashi A, Moir RD, Goldman RD, Poirier GG, Kaufmann SH and Earnshaw WC. . 1995 Proc. Natl. Acad. Sci. USA 92: 9042–9046.

  • Lebel M and Mes-Masson AM. . 1994 Exp. Cell Res. 213: 12–19.

  • Lebel M, Bertrand R and Mes-Masson AM. . 1996 Oncogene 12: 1127–1135.

  • Li CY, Lee JS, Ko YG, Kim JI and Seo JS. . 2000 J. Biol. Chem. 275: 25665–25671.

  • Li HL, Zhu H, Xu CJ and Yuan JY. . 1998 Cell 94: 491–501.

  • Luo X, Budihardjo I, Zou H, Slaughter C and Wang XD. . 1998 Cell 94: 481–490.

  • McBurney MW, Sutherland LC, Adra CN, Leclair B, Rudnicki MA and Jardine K. . 1991 Nucleic Acids Res. 19: 5755–5761.

  • McCarthy NJ, Whyte MK, Gilbert CS and Evan GI. . 1997 J. Cell Biol. 136: 215–227.

  • Mountz JD, Wu J, Zhou T and Hsu HC. . 1997 Immunol. Rev. 160: 19–30.

  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME and Dixit VM. . 1996 Cell 85: 817–827.

  • Nagata S. . 1997 Cell 88: 355–365.

  • Oberhammer FA, Hochegger K, Froschl G, Tiefenbacher R and Pavelka M. . 1994 J. Cell Biol. 126: 827–837.

  • Oyaizu H, Adachi Y, Taketani S, Tokunaga R, Fukuhara S and Ikehara S. . 1999 Mol. Cell Biol. Res. Commun. 2: 36–41.

  • Perkins CL, Fang G, Kim CN and Bhalla KN. . 2000 Cancer Res. 60: 1645–1653.

  • Pilon AA, Desjardins P, Hassell JA and Mes-Masson AM. . 1996 J. Virol. 70: 4457–4465.

  • Rassoulzadegan M, Cowie A, Carr A, Glaichenhaus N, Kamer R and Cuzin F. . 1982 Nature 300: 713–718.

  • Rasssoulzadegan M, Naghashfar Z, Cowie A, Carr A, Grisoni M, Kamer R and Cuzin F. . 1983 Proc. Natl. Acad. Sci. USA 80: 4354–4358.

  • Rathmell JC and Thompson CB. . 1999 Annu. Rev. Immunol. 17: 781–828.

  • Ray CA, Black RA, Kronheim SR, Greenstreet TA, Sleath PR, Salvesen GS and Pickup DJ. . 1992 Cell 69: 597–604.

  • Reed JC. . 1997 Semin. Hematol. 34: 9–19.

  • Resnick-Silverman L, Pang Z, Li G, Jha KK and Ozer HL. . 1991 J. Virol. 65: 2845–2852.

  • Riley MI, Yoo W, Mda NY and Folk WR. . 1997 J. Virol. 71: 6068–6074.

  • Rouquet N, Allemand I, Molina T, Bennoun M, Briand P and Joulin V. . 1995 Oncogene 11: 1061–1067.

  • Sakahira H, Enari M and Nagata S. . 1998 Nature 391: 96–99.

  • Saleh A, Srinivasula SM, Balkir L, Robbins PD and Alnemri ES. . 2000 Nat. Cell Biol. 2: 476–483.

  • Samali A and Orrenius S. . 1998 Cell Stress Chaperones 3: 228–236.

  • Sambrook J, Fritsch EF and Maniatis T. . 1989 Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.

  • Sane AT and Bertrand R. . 1999 Cancer Res. 59: 3565–3569.

  • Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH and Peter ME. . 1998 EMBO J. 17: 1675–1687.

  • Schett G, Steiner CW, Groger M, Winkler S, Graninger W, Smolen J, Xu Q and Steiner G. . 1999 FASEB J. 13: 833–842.

  • Schmitt E, Cimoli G, Steyaert A and Bertrand R. . 1998 Exp. Cell Res. 240: 107–121.

  • Schmitt E, Sane AT and Bertrand R. . 1999 Drug Resist Updates 2: 21–29.

  • Sheng Q, Denis D, Ratnofsky M, Roberts TM, DeCaprio JA and Schaffhausen B. . 1997 J. Virol. 71: 9410–9416.

  • Siegel RM and Fleisher TA. . 1999 J. Allergy Clin. Immunol. 103: 729–738.

  • Silver J, Schaffhausen B and Benjamin T. . 1978 Cell 15: 485–496.

  • Simonian PL, Grillot DAM and Nunez G. . 1997 Blood 90: 1208–1216.

  • Slinskey A, Barnes D and Pipas JM. . 1999 J. Virol. 73: 6791–6799.

  • Soeda E, Arrand JR, Smolar N, Walsh JE and Griffin BE. . 1980 Nature 283: 445–453.

  • Stennicke HR and Salvesen GS. . 1998 Biochim. Biophys. Acta 1387: 17–31.

  • Subramanian T, Tarodi B and Chinnadurai G. . 1995 Cell Growth Diff. 6: 131–137.

  • Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM and Kroemer G. . 1999 Nature 397: 441–446.

  • Takahashi H, Kobayashi H, Hashimoto Y, Matsuo S and Iizuka H. . 1995 J. Invest. Dermatol. 105: 810–815.

  • Teodoro JG and Branton PE. . 1997 J. Virol. 71: 1739–1746.

  • Tewari M, Telford WG, Miller RA and Dixit VM. . 1995 J. Biol. Chem. 270: 22705–22708.

  • Thompson CB. . 1995 Science 267: 1456–1462.

  • Vaux DL and Korsmeyer SJ. . 1999 Cell 96: 245–254.

  • Vayssier M and Polla BS. . 1998 Cell Stress Chaperones 3: 221–227.

  • Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV and Boldin MP. . 1999 Annu. Rev. Immunol. 17: 331–367.

  • Weigel TL, Lotze MT, Kim PK, Amoscato AA, Luketich JD and Odoux C. . 2000 J. Thorac. Cardiovasc. Surg. 119: 795–803.

  • Yasuda M, Theodorakis P, Subramanian T and Chinnadurai G. . 1998 J. Biol. Chem. 273: 12415–12421.

  • Yin XM, Oltval ZN and Korsmeyer SJ. . 1994 Nature 369: 321–323.

  • Young LS, Dawson CW and Elipooulos AG. . 1997 Br. Med. Bull. 53: 509–521.

  • Yuan J, Shaham S, Ledoux S, Ellis HM and Horvitz R. . 1993 Cell 75: 641–652.

  • Zheng DQ, Vayssiere JL, Petit PX, LeCoeur H, Spatz A, Mignotte B and Feunteun J. . 1994 Oncogene 9: 3345–3351.

  • Zhou Q, Snipas S, Orth K, Muzio M, Dixit VM and Salvesen GS. . 1997 J. Biol. Chem. 272: 7797–7800.

Download references

Acknowledgements

We thank L Champoux for technical assistance. We thank Dr L Masson for critical reading of the manuscript and scientific discussions. This research was funded by a Medical Research Council of Canada grant to A-M Mes-Masson. F Rodier is the recipient of an Institut du cancer de Montreal Canderel scholarship; M Bossolasco is the recipient of a studentship from the MRC; A-M Mes-Masson is the recipient of a Fonds de la recherche en santé au Québec (FRSQ) Chercheur National fellowship; R Bertrand is the recipient of an FRSQ Chercheur Junior II fellowship.

Author information

Authors and Affiliations

  1. Centre de recherche CHUM, Hôpital Notre Dame and Institut du cancer de Montréal, 1560 rue Sherbrooke est, Montréal, Québec, H2L 4M1, Canada

    F Rodier, R Bertrand, M Bossolasco & A-M Mes-Masson

  2. Département de médecine, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, Québec, H3C 3J7, Canada

    R Bertrand & A-M Mes-Masson

Authors
  1. F Rodier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Bertrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Bossolasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A-M Mes-Masson
    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

Rodier, F., Bertrand, R., Bossolasco, M. et al. Polyomavirus large T-antigen protects mouse cells from Fas-, TNF-α- and taxol-induced apoptosis. Oncogene 19, 6261–6270 (2000). https://doi.org/10.1038/sj.onc.1204015

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204015

Keywords

This article is cited by

Search

Advanced search

Quick links