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Gene Review

tAg  -  small t-antigen

Murine pneumotropic virus

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Disease relevance of tAg

  • BACKGROUND: Evidence that simian virus 40 (SV40) is associated with human mesotheliomas, osteosarcomas, and brain tumors suggests that a recombinant vaccine directed against lethal cancers expressing SV40 T antigen (Tag) could have clinical utility [1].
  • Transgenic animals harboring the early SV40 coding region (T/t-antigen) under the transcriptional control of the WAP promoter develop breast cancer after the first lactation period [2].
  • Transgenic mice expressing SV40 large T-antigen (Tag) oncogene in beta-cells develop tumours in a multi-stage progression from hyperplasia, angiogenesis, to solid encapsulated tumours [3].
  • Growth occurred more slowly and to lower titers than is seen with the prototypical PML JCV strain Mad-1, with relatively few cells containing viral T antigen (T-Ag) or viral capsid protein, Vp1 [4].
  • Cells transformed by Polyoma virus (Py) can undergo a high rate of excision or amplification of integrated viral DNA sequences, and these phenomena require the presence of homology (i.e., repeats) within the viral insertion as well as a functional viral large T antigen (T-Ag) [5].

High impact information on tAg

  • To determine whether the main role of large T-Ag in excision and amplification was replicative or recombination-promoting, we studied transformed rat cell lines containing tandem insertions of a ts-a Py molecule (encoding a thermolabile large T-Ag) with a deletion of the origin of viral DNA replication [5].
  • All G418-resistant clones analyzed readily amplified the integrated plasmid molecules when grown under conditions permissive for large T-Ag function, showing that these cells produced viral large T-Ag capable of promoting amplification in trans of DNA sequences containing the Py origin [5].
  • JCV encodes a "transforming" gene, T-antigen (T-Ag), which is believed to mediate the oncogenic potential of the virus [6].
  • Significant associations were observed between T-Ag expression and CIN in CRCs (P = .017) and between T-Ag expression and promoter methylation of multiple genes (P = .01) [6].
  • CONCLUSIONS: The association between T-Ag expression and promoter methylation in CRC suggests that this viral oncogene may induce methylator phenotype and that JCV may be involved in CRC through multiple mechanisms of genetic and epigenetic instability [6].

Chemical compound and disease context of tAg


Biological context of tAg

  • RESULTS: JCV T-Ag DNA sequences were found in 77% of the CRCs and 56% of these cancers (or 43% of the total) expressed T-Ag by IHC [6].
  • The ability of T antigen to functionally cooperate with Tst-1 was contained within its N-terminal region, shown by the fact that small tumor antigen (t antigen) could substitute for T antigen in transfection experiments [11].
  • We also report that the dominant inhibitory effect is caused by the DNA-dependent protein kinase (DNA-PK) which inactivates SV40 T antigen (TAg) by phosphorylation [12].
  • Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin [13].
  • BKV sequences and T antigen (Tag) are detected in several types of human neoplasms, although the viral load is generally low, with less than one copy of the viral genome per cell [14].

Anatomical context of tAg


Associations of tAg with chemical compounds

  • Upon acute infection, the frequency of mutation to 8AZ resistance was raised at most by two- to eightfold over the spontaneous frequency, and it was independent of the presence of a functional 90,000-molecular-weight T antigen or 20,000-molecular-weight t antigen or both [20].
  • When either this fraction (freed of urea) or NaDodSO4 gel-purified 865i t antigen (rendered free of detergent) was injected into untransformed rat cells, dissolution of intracellular actin cable networks was observed [19].
  • 2-difluoromethylornithine and dehydroepiandrosterone inhibit mammary tumor progression but not mammary or prostate tumor initiation in C3(1)/SV40 T/t-antigen transgenic mice [21].
  • Mutations were generated in Py T Ag whereby either or both threonines were replaced with alanine, generating T187A, T278A, and double-mutants (DM [T187A T278A]) mutant T Ags [22].
  • Prostatic lesions developed in these mice in a predictable and heritable manner, indicating that Neo did not alter Tag-induced prostate tumor development and progression [9].

Analytical, diagnostic and therapeutic context of tAg

  • PCR amplifications were performed for T-Ag sequences, and immunohistochemical (IHC) staining was performed to detect T-Ag expression [6].
  • When monoclonal antibodies or antisera against T antigen (T Ag) were added to SV40 chromosomes or when T Ag, both free and chromatin bound, was removed by immunoprecipitation with anti-T, the activity of the late promoter remained essentially unchanged [23].
  • TSTA is defined by SV40-specific transplantation immunity, whereas T-antigen (T-Ag) can be detected serologically by indirect immunofluorescence [24].
  • After gel filtration of such t antigen-enriched solutions, highly purified protein was obtained [19].
  • SV40 Tag expression was revealed by immunohistochemistry with the specific monoclonal antibody Pab 101 in PA thin sections with a highly sensitive technical approach which retrieved the nuclear viral oncoprotein in 26 out of 28 (93%) samples previously found SV40-positive by PCR [25].


  1. Induction of tumor antigen-specific immunity in vivo by a novel vaccinia vector encoding safety-modified simian virus 40 T antigen. Xie, Y.C., Hwang, C., Overwijk, W., Zeng, Z., Eng, M.H., Mulé, J.J., Imperiale, M.J., Restifo, N.P., Sanda, M.G. J. Natl. Cancer Inst. (1999) [Pubmed]
  2. SV40 T-antigen induces breast cancer formation with a high efficiency in lactating and virgin WAP-SV-T transgenic animals but with a low efficiency in ovariectomized animals. Santarelli, R., Tzeng, Y.J., Zimmermann, C., Guhl, E., Graessmann, A. Oncogene (1996) [Pubmed]
  3. Oncogenic co-operation in beta-cell tumorigenesis. Pelengaris, S., Khan, M. Endocr. Relat. Cancer (2001) [Pubmed]
  4. Propagation of archetype and nonarchetype JC virus variants in human fetal brain cultures: demonstration of interference activity by archetype JC virus. O'Neill, F.J., Greenlee, J.E., Dörries, K., Clawson, S.A., Carney, H. J. Neurovirol. (2003) [Pubmed]
  5. Amplification and excision of integrated polyoma DNA sequences require a functional origin of replication. Pellegrini, S., Dailey, L., Basilico, C. Cell (1984) [Pubmed]
  6. Association of JC virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers. Goel, A., Li, M.S., Nagasaka, T., Shin, S.K., Fuerst, F., Ricciardiello, L., Wasserman, L., Boland, C.R. Gastroenterology (2006) [Pubmed]
  7. Enhancement of transcription of the SV40 genome in mouse embryo cells by pretreatment with 5-iodo-2'-deoxyuridine. Suárez, H.G., Lange, M., Cassingena, R. J. Gen. Virol. (1981) [Pubmed]
  8. Molecular imaging of protein-protein interactions: controlled expression of p53 and large T-antigen fusion proteins in vivo. Luker, G.D., Sharma, V., Pica, C.M., Prior, J.L., Li, W., Piwnica-Worms, D. Cancer Res. (2003) [Pubmed]
  9. Androgen-dependent prostate epithelial cell selection by targeting ARR(2)PBneo to the LPB-Tag model of prostate cancer. Wang, Y., Kasper, S., Yuan, J., Jin, R.J., Zhang, J., Ishii, K., Wills, M.L., Hayward, S.W., Matusik, R.J. Lab. Invest. (2006) [Pubmed]
  10. Absence of SV-40 large T antigen (Tag) in malignant mesothelioma effusions: an immunocytochemical study. Simsir, A., Fetsch, P., Bedrossian, C.W., Ioffe, O.B., Abati, A. Diagn. Cytopathol. (2001) [Pubmed]
  11. The POU domain protein Tst-1 and papovaviral large tumor antigen function synergistically to stimulate glia-specific gene expression of JC virus. Renner, K., Leger, H., Wegner, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  12. Roles of replication protein A and DNA-dependent protein kinase in the regulation of DNA replication following DNA damage. Wang, Y., Zhou, X.Y., Wang, H., Huq, M.S., Iliakis, G. J. Biol. Chem. (1999) [Pubmed]
  13. Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells. Moll, J., Eibel, H., Botteri, F., Sansig, G., Regnier, C., van der Putten, H. Oncogene (1992) [Pubmed]
  14. Oncogenic transformation by BK virus and association with human tumors. Tognon, M., Corallini, A., Martini, F., Negrini, M., Barbanti-Brodano, G. Oncogene (2003) [Pubmed]
  15. Functional analysis of a conditionally transformed pancreatic beta-cell line. Fleischer, N., Chen, C., Surana, M., Leiser, M., Rossetti, L., Pralong, W., Efrat, S. Diabetes (1998) [Pubmed]
  16. Interleukin-10 is crucial for maintenance but not for developmental induction of peripheral T cell tolerance. Seewaldt, S., Alferink, J., Förster, I. Eur. J. Immunol. (2002) [Pubmed]
  17. T-antigen regulated expression reduces apoptosis of tag-transformed human myoblasts. Corti, S., Salani, S., Del Bo, R., Torrente, Y., Strazzer, S., Belicchi, M., Paganoni, S., Li, Z., Comi, G.P., Bresolin, N., Paulin, D., Scarlato, G. Cell. Mol. Life Sci. (2001) [Pubmed]
  18. Transgenic Bcl-2 expressed in photoreceptor cells confers both death-sparing and death-inducing effects. Quiambao, A.B., Tan, E., Chang, S., Komori, N., Naash, M.I., Peachey, N.S., Matsumoto, H., Ucker, D.S., Al-Ubaidi, M.R. Exp. Eye Res. (2001) [Pubmed]
  19. Purification of biologically active simian virus 40 small tumor antigen. Bikel, I., Roberts, T.M., Bladon, M.T., Green, R., Amann, E., Livingston, D.M. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  20. Relationship of simian virus 40 tumor antigens to virus-induced mutagenesis. Zannis-Hadjopoulos, M., Martin, R.G. Mol. Cell. Biol. (1983) [Pubmed]
  21. 2-difluoromethylornithine and dehydroepiandrosterone inhibit mammary tumor progression but not mammary or prostate tumor initiation in C3(1)/SV40 T/t-antigen transgenic mice. Green, J.E., Shibata, M.A., Shibata, E., Moon, R.C., Anver, M.R., Kelloff, G., Lubet, R. Cancer Res. (2001) [Pubmed]
  22. Cyclin-dependent kinase regulation of the replication functions of polyomavirus large T antigen. Li, H., Bhattacharyya, S., Prives, C. J. Virol. (1997) [Pubmed]
  23. Both trans-acting factors and chromatin structure are involved in the regulation of transcription from the early and late promoters in simian virus 40 chromosomes. Tack, L.C., Beard, P. J. Virol. (1985) [Pubmed]
  24. Detection of simian virus 40 T-antigen-related antigens by a 125I-protein A-binding assay and by immunofluorescence microscopy on the surface of SV40-transformed monolayer cells. Lange-Mutschler, J., Deppert, W., Hanke, K., Henning, R. J. Gen. Virol. (1981) [Pubmed]
  25. Simian virus 40 sequences and expression of the viral large T antigen oncoprotein in human pleomorphic adenomas of parotid glands. Martinelli, M., Martini, F., Rinaldi, E., Caramanico, L., Magri, E., Grandi, E., Carinci, F., Pastore, A., Tognon, M. Am. J. Pathol. (2002) [Pubmed]
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