Summary
Polyoma virus (Py) tumor (T) antigens are the proteins specified by the early region of the viral genome. They are responsible for most biological effects caused by this oncogenic virus, i.e. induction of tumors, cell transformation and most of the virus-induced events observed in productive and transforming infection. By immunoprecipitation with antitumor serum followed by gel electrophoresis three major Py T-antigens have been characterized: large Tantigen (IT) with an apparent MT of about 100 000, middle T-antigen (mT) of about 55 000 Mr and small T-antigen (sT) of about 23 000 Mr. In addition, there may exist one or more minor species by Py T-antigens. Analysis of the tryptic peptides showed that IT, mT and sT have a common N-terminal amino acid sequence, but differ from each other in the size and the sequence of the C-terminal part of the molecule as a consequence of different splicing of their mRNAs. With the nucleotide sequence of the Py genome being known, the coding regions for each of the Py T-antigens have been identified and consequently the amino acid sequence of IT, mT and sT was deduced. Cell fractionation experiments showed that the major part of 1T is located in the nucleus, mT was found in plasma membranes and sT is mainly present in the cytoplasm. Large T is a phosphoprotein and undergoes posttranslational modification. Two-dimensional gel electrophoresis of Py T-antigens revealed considerable charge heterogeneity particularly for mT and sT.
All Py transformed cell lines analyzed contained mT and sT. Large T was not detected in virtually all Py transformed mouse cell lines and in about one third of Py transformed rat and hamster cell lines. Instead of 1T often new immunoreactive proteins were found which are probably truncated forms of 1T. These and other recent results suggest that IT is required neither for initiation nor for maintenance of cell transformation. For tumor induction in hamsters, similar conclusions were reached from analysis of Py T-antigens and viral DNA sequences in cell lines derived from tumors that had been induced either by virus or by viral DNA digested with various restriction enzymes. Experiments done with several deletion mutants indicated that mT is required for cell transformation by Py. In a protein kinase assay done in vitro with Py T-antigen immunoprecipitates, a kinase activity associated with Py mT was found which phosphorylates tyrosine residues mainly of mT and less frequently of 1T and of rat immunoglobulins. In all transformation defective mutants, kinase activity measured by this assay was absent or strongly reduced.
In a concluding chapter I discuss the events occurring in wild-type virus and mutant infected cells trying to attribute specific functions to each of the three Py T-antigens. At least two functions are known for 1T, one is initiation of viral DNA replication, the other induces a mitotic response of the host cell, i.e. the events leading to and including host chromatin duplication. Middle T-antigen is certainly involved in cell transformation, possibly by its presence in the membrane. No function has been defined yet for sT. Since there are more virus-induced events observed in infected cells than Py T-antigens at least one of them must be a multifunctional protein.
Similar content being viewed by others
References
Gross, L., 1953. Proc. Soc. Exp. Biol. Med., 83, 414–421.
Stewart, S. E., Eddy, B. E., Gochenour, A. M., Borgese, N. G. and Grubbs, G. E., 1957. Virology, 3, 380–400.
Stewart, S. E., Eddy, B. E. and Borgese, N., 1958. J. Nat. Cancer Inst., 20, 1223–1236.
Di Mayorea, G. A., Eddy, B. E., Stewart, S. E., Hunter, W. S., Friend, C. and Bendich, A., 1959. Proc. Natl. Acad. Sci. USA, 45, 1805–1808.
Weil, R.; 1961. Virology, 14, 46–53.
Cremisi, C., Pignatti, P. F., Croissant, O. and Yaniv, M., 1976. J. Virol., 17, 204–211.
Finch, J. T. and Crawford, L. V., 1975. In Comprehensive Virology (Fraenkel-Conrat, H. and Wagner, R. R., editors) Vol. V, pp. 119–154, Plenum Press, New York.
Consigli, R. A. and Center, M. S., 1978. CRC Critical Reviews in Microbiology, 6, 263–299.
Brady, J. N., Winston, V. D. and Consigli, R. A., 1978. J. Virol., 27, 193–204.
Tooze, J., 1973. The Molecular Biology of Tumour Viruses (Cold Spring Harbor Laboratory).
Weil, R., 1978. Biochim. Biophys. Acta, 516, 301–388.
Seif, I., Khoury, G. and Dhar, R., 1979. Cell, 18, 963–977.
Friedmann, T., Esty, A., Laporte, P. and Deininger, D., 1979. Cell, 17, 715–724.
Deininger, P., Esty, A., Laporte, P. and Friedmann, T., 1979. Cell, 18, 771–779.
Soeda, E., Arrand, J. R., Griffin, B. E., 1979. Nucleic Acids Res., 7, 839–857.
Soeda, E., Arrand, J. R., Smolar, N., Walsh, J. E. and Griffin, B. E., 1980. Nature, 283, 445–453.
Griffin, B. E., Fried, M. and Cowie, A., 1974. Proc. Natl. Acad. Sci. USA, 71, 2077–2081.
Kamen, R., Lindstrom, D. M., Shure, H. and Old, R. W., 1974. Cold Spring Harbor Symp. Quant. Biol. 39, 187–198.
Siddell, S. G. and Smith, A. E., 1978. J. Virol., 27, 427–431.
Hunter, T. and Gibson, W., 1978. J. Virol., 28, 240–253.
Legon, S., Flavell, A. J., Cowie, A. and Kamen, R., 1979. Cell, 16, 373–388.
Manor, H., Wu, M., Baran, N. and Davidson, N., 1979. J. Virol., 32, 293–303.
Soeda, E., Arrand, J. R., Smolar, N. and Griffin, B. E., 1979. Cell, 17, 357–370.
Eddy, B. E., 1969. In Virology Monographs (Gard, S., Hallauer, C. and Meyer, K. F., editors) Vol. VII, pp. 1–114, Springer, Wien.
Weil, R., Salomon, C., May, E. and May, P., 1974. Cold Spring Harbor Symp. Quant. Biol., 39, 381–395.
Khandjian, E. W., Matter, J.-M., Leonard, N. and Weil, R., 1980. Proc. Natl. Acad. Sci. USA, 77, 1476–1480.
Fried, M., 1965. Virology, 25, 669–671.
Eckhart, W., 1974. Annu. Rev. Gen., 8, 301–317.
Miller, L. K. and Fried, M., 1976. J. Virol. 18, 824–832.
Francke, B. and Eckhart, W., 1973. Virology, 55, 127–135.
Oxman, M. N., Takemoto, K. K. and Eckhart, W., 1972. Virology, 49, 675–682.
Weil, R., Salomon, C., May, E. and May, P., 1974. In Viruses, Evolution and Cancer (Kurstak, E. and Maramorosch, K., editors) pp. 455–498. Academic Press, New York.
Cogen, B., 1978. Virology, 85, 222–230.
Fried, M., 1965. Proc. Natl. Acad. Sci. USA, 53, 486–491.
Eckhart, W., 1969. Virology, 38, 120–125.
Stoker, M. and Dulbecco, R., 1969. Nature, 223, 397–398.
Paulin, D. and Cuzin, F., 1975. J. Virol., 15 393–397.
Benjamin, T. L., 1970. Proc. Natl. Acad. Sci. USA, 7, 394–399.
Goldman, E. and Benjamin, T. L., 1975. Virology, 66, 372–384.
Staneloni, R. J., Fluck, M. M. and Benjamin, T. L., 1977. Virology, 77, 585–609.
Benjamin, T. L., Carmichael, G. G. and Schaffhausen, B. S., 1979. Cold Spring Harbor Symp. Quant. Biol., 44,
Schlegel, R. and Benjamin, T. L., 1978. Cell, 14, 587–599.
Feunteun, J., Sompayrac, L., Huck, M. and Benjamin, T., 1976. Proc. Natl. Acad. Sci. USA, 73, 4169–4173.
Eckhart, W., 1977. Virology, 77, 589–597.
Fluck, M. M., Staneloni, R. J. and Benjamin, T. L., 1977. Virology, 77, 610–624.
Fluck, M. M. and Benjamin, T. L., 1979. Virology, 96, 205–228.
Hattori, J., Carmichael, G. G. and Benjamin, T. L., 1979. Cell, 16, 505–513.
Carmichael, G. G. and Benjamin, T. L., 1980. J. Biol. Chem. 255, 230–235.
Griffin, B. E. and Maddock, C., 1979. J. Virol., 31, 645–656.
Wells, R. D., Hutchinson, M. A. and Eckhart, W., 1979. J. Virol., 32, 517–522.
Magnusson, G. and Berg, P., 1979. J. Virol., 32, 523–529.
Bendig, M. M. and Folk, W. R. 1979. J. Virol., 32, 530–535.
Bendig, M. M., Thomas, T. and Folk, W. R. 1980. J. Virol., 33, 1215–1220.
Anderson, D. M., Bendig, M. M. and Folk, W. R., 1978. Virology, 89, 637–642.
Huebner, R. J., Rowe, W. P., Turner, H. C. and Lane, W. T., 1963. Proc. Nad. Acad. Sci. USA, 50, 379–389.
Black, P. H., Rowe, W. P., Turner, H. C. and Huebner, R. J., 1963. Proc. Natl. Acad. Sci. USA, 50, 1148–1156.
Habel, K., 1965. Virology, 25, 55–61.
Takemoto, K. K., Malmgren, R. A. and Habel, K., 1966. Virology, 28, 485–488.
Levinthal, J. D., Wicker, R. and Cerottini, J. C., 1967. Virology, 31, 555–558.
Weil, R. and Kàra, J., 1970. Proc. Nod. Acad. Sci. USA, 67, 1011–1017.
Kamen, R. and Shure, H. 1976. Cell, 7, 361–371.
Tiirler, H., Salomon, C., Allet, B. and Weil, R., 1976. Proc. Natl. Acad. Sci. USA, 73, 1480–1484.
Salomon, C., Turler, H. and Weil, R. 1977. Nucleic Acids Res., 4, 1483–1503.
Graessmann, M., Graessmann, A., Niebel, J., Koch, H., Fogel, M. and Müller, C. 1975. Nature, 258, 756–758.
Graessmann, M. and Graessmann, A., 1976. Proc. Nati. Acad. Sci. USA, 73, 366–370.
Greenblatt, J. F., Allet, B. and Weil, R., 1976. J. Mol. Biol., 108, 361–379.
Rungger, D. and Turler, H., 1978. Proc. Natl. Acad. Sci. USA, 75, 6073–6077.
Ito, Y., Spurr, N. and Dulbecco, R., 1977. Proc. Natl. Acad. Sci. USA, 74, 1259–1263.
Türler, H. and Salomon, C., 1977. INSERM Colloqu., 69, 131–144.
Schaffhausen, B. S., Silver, J. E. and Benjamin, T. L., 1978. Proc. Natl. Acad. Sci. USA, 75, 79–83.
Hutchinson, M. A., Hunter, T. and Eckhart, W., 1978. Cell, 15, 65–77.
Simmons, D. T., Chang, C. and Martin, M. A., 1979. J. Virol., 29, 881–887.
Kessler, S. W., 1975. J. Immunol., 115, 1617–1624.
Schwyzer, M., 1977. INSERM Colloqu., 69, 63–68.
Smart, J. E. and Ito, Y., 1978. Cell, 15, 1427–1437.
Silver, J., Schaffhausen, B. and Benjamin, T., 1978. Cell, 15, 485–496.
Ito, Y. and Spurr, N., 1979. Cold Spring Harbor Symp. Quant. Biol., 44, in press.
Hunter, T., Hutchinson, M. A. and Eckhart, W., 1978. Proc. Natl. Acad. Sci. USA, 75, 5917–5921.
Mellor, A. and Smith, A. E., 1978. J. Virol., 28, 992–996.
Berk, A. J. and Sharp, P. A., 1977. Cell, 12, 721–732.
Favaloro, J., Treisman, R. and Kamen, R., 1980. Methods Enzymol., 65, 718–749.
Kamen, R., Favaloro, J., Parker, J., Treisman, R., Lania, L., Fried, M. and Mellor, A., 1979. Cold Spring Harbor Symp. Quant. Biol., 44, in press.
Fiers, W., Contreras, R., Haegeman, G., Rogiers, R., Van de Voorde, A., Van Heuverswyn, H., Van Herreweghe, J., Volckaert, G. and Ysebaert, M., 1978. Nature, 273, 113–120.
Reddy, V. B., Thimmappaya, B., Dhar, R., Subramanian, K. N., Zain, B. S., Pan, J., Ghosh, P. K., Celma, M. L. and Weissman, S. M., 1978. Science, 200, 494–502.
Dhar, R., Lai, C. J. and Khoury, G., 1978. Cell, 13, 345–358.
Yang, R. C. A. and Wu, R. 1979. Science, 206, 456–462.
Friedmann, T., Doolittle, R. F. and Walter, G., 1978. Nature, 274, 291–293.
Ferguson, J. and Davis, R. W., 1975. J. Mol. Biol., 94, 135–149.
Hunter, T., Hutchinson, M. A., Eckhart, W., Friedmann, T., Esty, A., Laporte, P. and Deininger, P., 1979. Cold Spring Harbor Symp. Quant. Biol., 44,
Hunter, T., Hutchinson, M. A., Eckhart, W., Friedmann, T., Esty, A., Laporte, P. and Deininger, P., 1979. Nucleic Acids. Res. 7, 2275–2288.
Ito, Y., Spurr, N. and Griffin, B. E. 1980, J. Virol., 35, 219–232.
Ito, Y., 1979. Virology, 98, 261–266.
Lai, C. J. and Nathans, D., 1975. Virology, 66, 70–81.
Ito, Y., Brocklehurst, J. R. and Dulbecco, R., 1977. Proc. Natl. Acad. Sci. USA, 74, 4666–4670.
Rey-Bellet, V. and Tiirler, H., 1978. Experientia, 34, 953 (abstract).
Brunette, D. M. and Till, J. E., 1971. J. Membrane Biol., 5, 215–224.
Wintersberger, E. and Wintersberger, U., 1976. J. Virol., 19, 291–295.
Tiirler, H. and Salomon, C., 1978. Experientia, 34, 959 (abstract).
O'Farrell, P. H. and O'Farrell, P. Z., 1977. Methods Cell Biol., 16, 407–420.
Crawford, L. V. and O'Farrell, P. Z., 1979. J. Virol., 29, 587–596.
Riordan, J. F. and Vallee, B. L., 1967. Methods Enzymol., 11, 541–548.
Smyth, D. G., Nagamatsu, A. and Fruton, J. S., 1960. J. Am. Chem. Soc. 82, 4600–4604.
Benjamin, T. L., Schaffhausen, B. S. and Silver, J. E., 1979. J. Supramol. Struct., 12, 127–137.
Birg, F., Dulbecco, R., Fried, M. and Kamen, R., 1979. J. Virol., 29, 633–648.
Prasad, I., Zouzias, D., Basilico, C., 1976. J. Virol., 18, 436–444.
Lania, L., Gandini-Attardi, D., Griffiths, M., Cooke, B., De Cicco, D. and Fried, M., 1980. Virology, 101, 217–232.
Lania, L., Hayday, A., Bjursell, G., Gandini-Attardi, D. and Fried, M., 1979. Cold Spring Harbor Symp. Quant. Biol., 44, in press.
Griffin, B. E., Ito, Y., Novak, U., Spurr, N., Dilworth, S., Smolar, N., Pollack, R., Smith, K. and Rifkin, D. B., 1979. Cold Spring Harbor Symp. Quant. Biol., 44, in press.
Hassell, J. A., Topp, W. C., Rifkin, D. B. and Moreau, P. E., 1980. Proc. Natl. Acad. Sci. USA, 77, 3978–3982.
Novak, U., Dilworth, S. M. and Griffin, B. E., 1980. Proc. Natl. Acad. Sci. USA, 77, 3278–3282.
Lania, L., Griffiths, M., Cooke, B., Ito, Y. and Fried, M., 1979. Cell, 18, 793–802.
Israel, M. A., Chan, H. W., Hourihan, S. L., Rowe, W. P. and Martin, M. A., 1979. J. Virol., 29, 990–996.
Israel, M. A., Simmons, D. T., Hourihan, S. L., Rowe, W. P. and Martin, M. A., 1979. Proc. Nati. Acad. Sci. USA, 76, 3713–3716.
Israel, M. A., Chowdhury, K., Ramseur, J., Chandrasekaran, K., Vanderryn, D. F. and Martin, M. A., 1979. Cold Spring Harbor Symp. Quant. Biol., 44, in press.
Israel, M. A., Chan, H. W., Rowe, W. P. and Martin, M. A., 1979. Science, 203, 883–887.
Smith, A. E., Smith, R., Griffin, B. and Fried, M., 1979. Cell, 18, 915–924.
Eckhart, W., Hutchinson, M. A. and Hunter, T., 1979. Cell, 18, 925–933.
Schaffhausen, B. S. and Benjamin, T. L., 1979. Cell, 18, 934–946.
Collett, M. S., Erikson, E. and Erikson, R. L., 1979. J. Virol., 29, 770–781.
Hunter, T. and Sefton, B. M., 1980. Proc. Natl. Acad. Sci. USA, 77, 1311–1315.
Collett, M. S. and Erikson, R. L., 1978. Proc. Natl. Acad. Sci. USA, 75, 2021–2024.
Levinson, A. D., Oppermann, H., Levintow, L., Varmus, H. E. and Bishop, J. M., 1978. Cell, 15, 561–572.
Rübsamen, H., Friis, R. R. and Bauer, H., 1979. Proc. Natl. Acad. Sci. USA, 76, 967–971.
Spector, D. H., Varmus, H. E. and Bishop, J. M., 1978. Proc. Natl. Acad. Sci. USA, 75, 4102–4106.
Lassam, N. J., Bayley, S. T., Graham, F. L. and Branton, P. E., 1979. Nature, 277, 241–243.
Raska, K., Geis, A. and Föhring, B., 1979. Virology, 99, 174–178.
Griffin, J. E., Spangler, G. and Livingston, D. M., 1979. Proc. Natl. Acad. Sci. USA, 76, 2610–2614.
Giacherio, D. and Hager, L. P., 1979. J. Biol. Chem., 254, 8113–8116.
Tjian, R. and Robbins, A., 1979. Proc. Natl. Acad. Sci. USA, 76, 610–614.
Paulin, D., Gaudray, P. and Cuzin, F., 1975. Biochem. Biophys. Res. Comm., 65, 1418–1426.
Gaudray, P., Clertant, P. and Cuzin, F., 1977. INSERM Colloq., 69, 121–130.
Tjian, R., 1978. Cell, 13, 165–179.
Mackay, R. L. and Consigh, R. A., 1976. J. Virol., 19, 620–636.
Goldstein, D. A., Hall, M. R. and Meinke, W., 1973. J. Virol., 12, 887–900.
Seebeck, T. and Weil, R., 1974. J. Virol., 13, 567–576.
Acheson, N. H. 1976. Cell, 8, 1–12.
Seehafer, J. G. and Weil, R., 1974. Virology, 58, 75–85.
Türler, H., 1977. J. Virol. 23, 272–285.
.Irlin, F. S., 1967. Virology, 32, 725–728.
Barra, Y., Berebbi, M., Reynier, M. and Meyer, G., 1977. INSERM Colloqu., 69, 337–348.
Häyry, P. and Defendi, V., 1970. Virology, 41, 22–29.
Levine, A. S., Oxman, M. N., Henry, P. H., Levin, M. J., Diamandopoulos, G. T. and Enders, J. F., 1970. J. Virol. 6, 199–207.
Berman, L. D., 1972. Int. J. Cancer, 10, 326–330.
Sjögren, H. O., 1965. Progr. Exp. Tumor Res., 6, 289–322.
Schaffhausen, B. S. and Benjamin, T. L., 1976. Proc. Natl. Acad. Sci. USA, 73, 1092–1096.
Basilico, C. and Wang, R., 1971. Nature New Biology. 230, 105–107.
Shenk, T. E., Carbon, J. and Berg, P., 1976. J. Virol., 18, 664–671.
Weil, R., Türler, H., Léonard, N. and Ahmad-Zadeh, C., 1977. INSERM Colloqu., 69, 263–280.
Rigby, P., 1979. Nature, 282, 781–784.
Seif, R. and Cuzin, F., 1977. J. Virol., 24, 721–728.
Rassoulzadegan, M., Seif, R. and Cuzin, F., 1978. J. Virol., 28, 421–426.
Rassoulzadegan, M., Mougneau, E., Berbal, P., Gaudray, P., Birg, F. and Cuzin, F., 1979. Cold Spring Harbor Symp. Quant. Biol., 44, in press.
Ossowski, L., Quigley, J. P., Kellerman, G. M. and Reich, E. 1973. J. Exp. Med., 138, 1056–1064.
Pollack, R., Risser, R., Conlon, S. and Rifkin, D., 1974. Proc. Natl. Acad. Sci. USA, 71, 4792–4796.
Rogers, M. J., Law, L. W. and Appella, E., 1977. INSERM Colloqu., 69, 349–356.
Risser, R., Rifkin, D. and Pollack, R., 1974. Cold Spring Harbor Symp. Quant. Biol., 39, 317–324.
Tjian, R., Fey, G. and Graessmann, A., 1978. Proc. Natl. Acad. Sci. USA, 75, 1279–1283.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Türler, H. The tumor antigens and the early functions of polyoma virus. Mol Cell Biochem 32, 63–93 (1980). https://doi.org/10.1007/BF00227801
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00227801