1887

Abstract

Papovavirus tumour antigens have been widely used to study cell growth regulation in cultured cells. We investigated the role of mouse polyomavirus T antigens, small-, middle- and large-T, in stimulating growth-arrested REF52 fibroblasts to enter the S phase. Microinjecting cells with cDNAs encoding the various T antigens showed: first, that middle-T expression blocked cell cycle stimulation by serum; second, that middle-T-arrested cells were released into the S phase upon coexpression of small-T; third, that expression of middle-T together with large-T committed resting cells to enter the cell cycle even in the absence of serum. Our data indicate that extensive cooperation among polyomavirus T antigens is essential for T antigen-mediated cell cycle stimulation in growth-arrested cells. In addition, the data suggest a new role for small-T in signalling to mitogenic pathways.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-11-2917
1999-11-01
2020-01-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/11/0802917a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-11-2917&mimeType=html&fmt=ahah

References

  1. Cayla, X. , Ballmer-Hofer, K. , Merlevede, W. & Goris, J. ( 1993; ). Phosphatase 2A associated with polyomavirus small-T or middle-T antigen is an okadaic acid-sensitive tyrosyl phosphatase. European Journal of Biochemistry 214, 281-286.[CrossRef]
    [Google Scholar]
  2. Cress, W. D. & Nevins, J. R. ( 1996; ). Use of the E2F transcription factor by DNA tumor viruses regulatory proteins. Current Topics in Microbiology and Immunology 208, 63-78.
    [Google Scholar]
  3. Dilworth, S. M. ( 1995; ). Polyoma virus middle T antigen: meddler or mimic? Trends in Microbiology 3, 31-35.[CrossRef]
    [Google Scholar]
  4. Dilworth, S. M. & Horner, V. P. ( 1993; ). Novel monoclonal antibodies that differentiate between the binding of pp60c-src or protein phosphatase 2A by polyomavirus middle T antigen. Journal of Virology 67, 2235-2244 .
    [Google Scholar]
  5. Dunant, N. & Ballmer-Hofer, K. ( 1997; ). Signalling by Src family kinases: lessons learnt from DNA tumour viruses. Cellular Signalling 9, 385-393.[CrossRef]
    [Google Scholar]
  6. Frost, J. A. , Alberts, A. S. , Sontag, E. , Guan, K. , Mumby, M. C. & Feramisco, J. R. ( 1994; ). Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity. Molecular and Cellular Biology 14, 6244-6252 .[CrossRef]
    [Google Scholar]
  7. Hall, P. & Lane, D. P. ( 1997; ). Tumor suppressors: a developing role for p53? Current Biology 7, R144-R147.[CrossRef]
    [Google Scholar]
  8. Hirakawa, T. & Ruley, H. E. ( 1988; ). Rescue of cells from ras oncogene-induced growth arrest by a second, complementing, oncogene. Proceedings of the National Academy of Sciences, USA 85, 1519-1523 .[CrossRef]
    [Google Scholar]
  9. Ishizaka, Y. , Chernov, M. V. , Burns, C. M. & Stark, G. R. ( 1995; ). p53-dependent growth arrest of REF52 cells containing newly amplified DNA. Proceedings of the National Academy of Sciences, USA 92, 3224-3228 .[CrossRef]
    [Google Scholar]
  10. Land, H. , Parada, L. F. & Weinberg, R. A. ( 1983; ). Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304, 596-602.[CrossRef]
    [Google Scholar]
  11. Levine, A. J. ( 1997; ). p53, the cellular gatekeeper for growth and division. Cell 88, 323-331.[CrossRef]
    [Google Scholar]
  12. Lin, A. W. , Barradas, M. , Stone, J. C. , van Aelst, L. , Serrano, M. & Lowe, S. W. ( 1998; ). Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes & Development 12, 3008-3019 .[CrossRef]
    [Google Scholar]
  13. Messerschmitt, A. , Disela, C. , Dilworth, S. , Marti, A. G. & Ballmer-Hofer, K. ( 1996; ). Polyomavirus middle-T antigen lacking a membrane anchor sequence accumulates in the nucleus. Journal of General Virology 77, 17-26.[CrossRef]
    [Google Scholar]
  14. Messerschmitt, A. , Dunant, N. M. & Ballmer-Hofer, K. ( 1997; ). DNA tumor viruses and Src family tyrosine kinases, an intimate relationship. Virology 227, 271-280.[CrossRef]
    [Google Scholar]
  15. Mor, O. , Read, M. & Fried, M. ( 1997; ). p53 in polyoma virus transformed REF52 cells. Oncogene 15, 3113-3119 .[CrossRef]
    [Google Scholar]
  16. Pallas, D. C. , Shahrik, L. K. , Martin, B. L. , Jaspers, S. , Miller, T. B. , Brautigan, D. L. & Roberts, T. M. ( 1990; ). Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A. Cell 60, 167-176.[CrossRef]
    [Google Scholar]
  17. Parada, L. F. , Land, H. , Weinberg, R. A. , Wolf, D. & Rotter, V. ( 1984; ). Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature 312, 649-651.[CrossRef]
    [Google Scholar]
  18. Raptis, L. , Lamfrom, H. & Benjamin, T. L. ( 1985; ). Regulation of cellular phenotype and expression of polyomavirus middle T antigen in rat fibroblasts. Molecular and Cellular Biology 5, 2476-2486.
    [Google Scholar]
  19. Rassoulzadegan, M. , Cowie, A. , Carr, A. , Glaichenhaus, N. , Kamen, R. & Cuzin, F. ( 1982; ). The roles of individual polyoma virus early proteins in oncogenic transformation. Nature 300, 713-718.[CrossRef]
    [Google Scholar]
  20. Ridley, A. J. , Paterson, H. F. , Noble, M. & Land, H. ( 1988; ). Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation. EMBO Journal 7, 1635-1645.
    [Google Scholar]
  21. Serrano, M. , Lin, A. W. , McCurrach, M. E. , Beach, D. & Lowe, S. W. ( 1997; ). Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593-602.[CrossRef]
    [Google Scholar]
  22. Sewing, A. , Wiseman, B. , Lloyd, A. C. & Land, H. ( 1997; ). High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1. Molecular and Cellular Biology 17, 5588-5597 .
    [Google Scholar]
  23. Sontag, E. , Fedorov, S. , Kamibayashi, C. , Robbins, D. , Cobb, M. & Mumby, M. ( 1993; ). The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation. Cell 75, 887-897.[CrossRef]
    [Google Scholar]
  24. Strauss, M. , Hering, S. , Lubbe, L. & Griffin, B. E. ( 1990; ). Immortalization and transformation of human fibroblasts by regulated expression of polyoma virus T antigens. Oncogene 5, 1223-1229.
    [Google Scholar]
  25. Teodoro, J. G. & Branton, P. E. ( 1997; ). Regulation of apoptosis by viral gene products. Journal of Virology 71, 1739-1746 .
    [Google Scholar]
  26. Urich, M. , El Shemerly, M. Y. , Besser, D. , Nagamine, Y. & Ballmer-Hofer, K. ( 1995; ). Activation and nuclear translocation of mitogen-activated protein kinases by polyomavirus middle-T or serum depend on phosphatidylinositol 3-kinase. Journal of Biological Chemistry 270, 29286-29292 .[CrossRef]
    [Google Scholar]
  27. Walter, G. , Ruediger, R. , Slaughter, C. & Mumby, M. ( 1990; ). Association of protein phosphatase 2A with polyoma virus medium tumor antigen. Proceedings of the National Academy of Sciences, USA 87, 2521-2525 .[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-11-2917
Loading
/content/journal/jgv/10.1099/0022-1317-80-11-2917
Loading

Data & Media loading...

Most cited articles

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error