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Gene Review

TAg  -  large T-antigen

Murine pneumotropic virus

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Disease relevance of TAg

  • Analysis of the DNA sequences encoding the T-ag carboxy terminus revealed sequence variation among the tumors, as observed previously in viral DNA associated with human brain tumors [1].
  • SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes [1].
  • We have previously demonstrated the presence of JCV-TAg in colorectal cancers, in adjacent normal colonic mucosa from these patients, and in the human colon cancer cell line SW480 [2].
  • Using a double transgenic murine hepatic tumor model, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP-1) blocks liver hyperplasia during tumor development, despite TAg-mediated reactivation of IGF-II [3].
  • Immunofluorescence and Western blot were performed for TAg, viral capsid proteins, and nuclear beta-catenin expressions, whereas coimmunoprecipitation was used to detect protein interactions [4].

Psychiatry related information on TAg

  • Carbohydrate-mediated suppression of TAg resulted in slow hepatic growth that progressed to focal hepatocellular carcinoma (HCC) after a long latency period [5].
  • Three transformed lines (COS-1, -3, -7) were established and found to contain T antigen; retain complete permissiveness for lytic growth of SV40; support the replication of tsA209 virus at 40 degrees C; and support the replication of pure populations of SV40 mutants with deletions in the early region [6].

High impact information on TAg

  • Crossbred mice carrying the Tag oncogene and a disruption of either the paternal or maternal allele of IGF2 reveal that both alleles are co-activated early during tumour development, and that each contributes to malignant hyperproliferation and consequent tumour volume [7].
  • Tumors from 31 children--20 with choroid plexus neoplasms and 11 with ependymomas--were evaluated for the presence of polyomavirus T-antigen gene sequences by means of amplification with the polymerase chain reaction [8].
  • Half of the choroid plexus tumors and most of the ependymomas that we studied contained and expressed a segment of T-antigen gene related to SV40 [8].
  • Binding and unwinding--how T antigen engages the SV40 origin of DNA replication [9].
  • The inhibition is neither a direct nor an indirect result of T antigen binding to DNA, because the hMT IIA promoter lacks T antigen binding sites [10].

Chemical compound and disease context of TAg


Biological context of TAg

  • SSCP and sequencing analysis confirmed the amplification of viral quasispecies and the authenticity of TAg sequences [2].
  • The results demonstrate that RPA and DNA-PK are involved in the regulation of viral DNA replication after DNA damage and suggest that analogous processes regulate cellular DNA replication with the DNA-PK targeting the functional homologues of TAg [16].
  • To understand this species specificity, we evaluated human and yeast RPA in enzymatic assays with SV40 T antigen (TAg) and human DNA polymerase alpha/primase, the factors essential for initiation of SV40 DNA replication [17].
  • In situ hybridisation studies in the hair follicle using histone H3 as a cell proliferation marker suggested that cell proliferation had ceased prior to commencement of K2.10-TAg expression and was not re-established in the differentiating cortical cells [18].
  • Hence, TAg was unable to induce cell immortalisation at that stage of cortical cell differentiation [18].

Anatomical context of TAg


Associations of TAg with chemical compounds

  • SV40 chromatin extracted from 42 h post-infected cells by a modification of the standard Triton X-100-EDTA procedure and purified on neutral sucrose gradients was partially immunoprecipitable by a specific SV40 T-antigen (T-Ag) antiserum [22].
  • 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 [23].
  • In a recently developed cell line, denoted betaTC-tet, derived from transgenic mice expressing the SV40 T antigen (Tag) under control of the tetracycline (Tc) gene regulatory system, growth arrest can be induced by shutting off Tag expression in the presence of Tc [24].
  • Activation of the Cre recombinase by 4-hydroxy-tamoxifen induced SV40 T-Ag excision, leading to the death of cells expressing Cre recombinase [25].
  • Treatment of the NPCs with 4 M guanidine-hydrochloride, however, resulted in a substantial decrease in the amount of SV40 (I) and (II) DNA associated with T antigen [13].

Other interactions of TAg

  • 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 [26].
  • When antibody against viral capsid protein Vp1 or Vp3 was introduced into the cytoplasm, the nuclear accumulation of T antigen was not observed in cells either infected or cytoplasmically injected with virion [27].
  • The NCCRs of the several Indian endemic strains were analysed by sequencing PCR products, amplified directly from urine samples, with oligonucleotide primers designed from the constant region of T-Antigen and VP2 coding sequences [28].

Analytical, diagnostic and therapeutic context of TAg


  1. SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Lednicky, J.A., Stewart, A.R., Jenkins, J.J., Finegold, M.J., Butel, J.S. Int. J. Cancer (1997) [Pubmed]
  2. JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Ricciardiello, L., Laghi, L., Ramamirtham, P., Chang, C.L., Chang, D.K., Randolph, A.E., Boland, C.R. Gastroenterology (2000) [Pubmed]
  3. Insulin-like growth factor II signaling in neoplastic proliferation is blocked by transgenic expression of the metalloproteinase inhibitor TIMP-1. Martin, D.C., Fowlkes, J.L., Babic, B., Khokha, R. J. Cell Biol. (1999) [Pubmed]
  4. Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus. Ricciardiello, L., Baglioni, M., Giovannini, C., Pariali, M., Cenacchi, G., Ripalti, A., Landini, M.P., Sawa, H., Nagashima, K., Frisque, R.J., Goel, A., Boland, C.R., Tognon, M., Roda, E., Bazzoli, F. Cancer Res. (2003) [Pubmed]
  5. Induction of hepatocyte proliferation and death by modulation of T-Antigen expression. Comerford, S.A., Clouthier, D.E., Hinnant, E.A., Hammer, R.E. Oncogene (2003) [Pubmed]
  6. SV40-transformed simian cells support the replication of early SV40 mutants. Gluzman, Y. Cell (1981) [Pubmed]
  7. Deregulation of both imprinted and expressed alleles of the insulin-like growth factor 2 gene during beta-cell tumorigenesis. Christofori, G., Naik, P., Hanahan, D. Nat. Genet. (1995) [Pubmed]
  8. DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. Bergsagel, D.J., Finegold, M.J., Butel, J.S., Kupsky, W.J., Garcea, R.L. N. Engl. J. Med. (1992) [Pubmed]
  9. Binding and unwinding--how T antigen engages the SV40 origin of DNA replication. Borowiec, J.A., Dean, F.B., Bullock, P.A., Hurwitz, J. Cell (1990) [Pubmed]
  10. Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen. Mitchell, P.J., Wang, C., Tjian, R. Cell (1987) [Pubmed]
  11. Direct luteinizing hormone action triggers adrenocortical tumorigenesis in castrated mice transgenic for the murine inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene. Rilianawati, n.u.l.l., Paukku, T., Kero, J., Zhang, F.P., Rahman, N., Kananen, K., Huhtaniemi, I. Mol. Endocrinol. (1998) [Pubmed]
  12. Cell lines of the pituitary gonadotrope lineage derived by targeted oncogenesis in transgenic mice. Windle, J.J., Weiner, R.I., Mellon, P.L. Mol. Endocrinol. (1990) [Pubmed]
  13. Salt-resistant association of simian virus 40 T antigen with simian virus 40 DNA in nucleoprotein complexes. Rudolph, K., Mann, K. J. Virol. (1983) [Pubmed]
  14. Biochemical characterization and localization of JC virus large T antigen phosphorylation domains. Swenson, J.J., Frisque, R.J. Virology (1995) [Pubmed]
  15. The G gamma / T-15 transgenic mouse model of androgen-independent prostate cancer: target cells of carcinogenesis and the effect of the vitamin D analogue EB 1089. Perez-Stable, C.M., Schwartz, G.G., Farinas, A., Finegold, M., Binderup, L., Howard, G.A., Roos, B.A. Cancer Epidemiol. Biomarkers Prev. (2002) [Pubmed]
  16. 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]
  17. An interaction between replication protein A and SV40 T antigen appears essential for primosome assembly during SV40 DNA replication. Melendy, T., Stillman, B. J. Biol. Chem. (1993) [Pubmed]
  18. Targeted expression of SV40 T antigen in the hair follicle of transgenic mice produces an aberrant hair phenotype. Keough, R., Powell, B., Rogers, G. J. Cell. Sci. (1995) [Pubmed]
  19. Transgene expression and repression in transgenic rats bearing the phosphoenolpyruvate carboxykinase-simian virus 40 T antigen or the phosphoenolpyruvate carboxykinase-transforming growth factor-alpha constructs. Haas, M.J., Dragan, Y.P., Hikita, H., Shimel, R., Takimoto, K., Heath, S., Vaughan, J., Pitot, H.C. Am. J. Pathol. (1999) [Pubmed]
  20. Free and viral chromosome-bound simian virus 40 T antigen: changes in reactivity of specific antigenic determinants during lytic infection. Tack, L.C., Wright, J.H., Gurney, E.G. J. Virol. (1986) [Pubmed]
  21. High incidence of BK virus large-T-antigen-coding sequences in normal human tissues and tumors of different histotypes. De Mattei, M., Martini, F., Corallini, A., Gerosa, M., Scotlandi, K., Carinci, P., Barbanti-Brodano, G., Tognon, M. Int. J. Cancer (1995) [Pubmed]
  22. Localization of T-antigen on simian virus 40 minichromosomes by immunoelectron microscopy. Harper, F., Florentin, Y., Puvion, E. EMBO J. (1984) [Pubmed]
  23. Relationship of simian virus 40 tumor antigens to virus-induced mutagenesis. Zannis-Hadjopoulos, M., Martin, R.G. Mol. Cell. Biol. (1983) [Pubmed]
  24. 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]
  25. Long-term controlled immortalization of a primate hepatic progenitor cell line after Simian virus 40 T-Antigen gene transfer. Delgado, J.P., Parouchev, A., Allain, J.E., Pennarun, G., Gauthier, L.R., Dutrillaux, A.M., Dutrillaux, B., Di Santo, J., Capron, F., Boussin, F.D., Weber, A. Oncogene (2005) [Pubmed]
  26. 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]
  27. Association with capsid proteins promotes nuclear targeting of simian virus 40 DNA. Nakanishi, A., Clever, J., Yamada, M., Li, P.P., Kasamatsu, H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  28. High reactivation of BK virus variants in Asian Indians with renal disorders and during pregnancy. Bhattacharjee, S., Chakraborty, T. Virus Genes (2004) [Pubmed]
  29. Large T antigen coding sequences of two DNA tumor viruses, BK and SV40, and nonrandom chromosome changes in two glioblastoma cell lines. Tognon, M., Casalone, R., Martini, F., De Mattei, M., Granata, P., Minelli, E., Arcuri, C., Collini, P., Bocchini, V. Cancer Genet. Cytogenet. (1996) [Pubmed]
  30. Protein-protein interactions of the primase subunits p58 and p48 with simian virus 40 T antigen are required for efficient primer synthesis in a cell-free system. Weisshart, K., Förster, H., Kremmer, E., Schlott, B., Grosse, F., Nasheuer, H.P. J. Biol. Chem. (2000) [Pubmed]
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