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Gene Review

SV40gp6  -  large T antigen

Simian virus 40

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Disease relevance of SV40gp6


High impact information on SV40gp6

  • We have purified two major polypeptides of 54 and 56 kd from bovine erythrocytes that specifically bind the nuclear location sequence (NLS) of the SV40 large T antigen [6].
  • Since it was immortalized using the temperature-sensitive allele tsA58 of SV40 large T antigen, these cells grow continuously at 33 degrees C, but not at 39 degrees C, the body temperature of rodents [7].
  • SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family [8].
  • Mapping of an amino acid sequence responsible for the nuclear localization of the c-abl (IV) protein reveals a nuclear localization signal similar to that of SV40 large T antigen [9].
  • A biochemical role for SV40 small t antigen (t) in the viral infectious cycle that would explain the strong conservation of t structure among papovaviruses and its role as a helper of SV40 large T antigen function in the viral transforming process is not understood [10].

Chemical compound and disease context of SV40gp6


Biological context of SV40gp6


Anatomical context of SV40gp6


Associations of SV40gp6 with chemical compounds

  • This transversion resulted in the creation of a new RsaI cleavage site in the tsA1499 DNA and predicts an arginine-to-threonine substitution at amino acid position 186 in the mutant large T antigen [23].
  • Stringent selection for neo expression by homologous recombination (3 of 11 correctly targeted) was achieved by fusing the SV40 large T antigen gene, in frame, to neo in a promoterless construct, such that G418 resistance depended on endogenous promoter function and read-through transcription [24].
  • The structure also shows that LTag binding induces dramatic conformational changes at the DNA-binding area of p53, which is achieved partially through an unusual "methionine switch" within p53 [25].
  • The amino acid sequence displays two glutamic acid-rich domains, which are probably involved in the interaction with the histones, and a putative nuclear targeting signal with high homology to that of the SV40 large T-antigen which is located near the carboxy terminus.(ABSTRACT TRUNCATED AT 250 WORDS)[26]
  • In the MMR-proficient cells, activation of the MNNG-induced G(2)/M checkpoint was accompanied by phosphorylation of p53, but the cell death pathway was p53 independent, as the latter polypeptide is functionally inactivated in these cells by SV40 large T antigen [27].

Regulatory relationships of SV40gp6


Analytical, diagnostic and therapeutic context of SV40gp6

  • Using electron microscopy, we show that the N-terminal part of LTag that includes the origin-binding domain does not present a stable quaternary structure in single hexamers [19].
  • The amount of telomerase activity increased during passage in cell culture and appeared to parallel increases in the cellular amounts of the SV40 large T-antigen [29].
  • Crude and highly purified SV40 large T antigen has been found to exist in forms of various sizes Immunoreactive structures of 5.5S (80-85 kd), 7S (or approximately 150 kd) and 15.5S (325-340 kd) have been identified by zonal sedimentation and gel filtration [30].
  • A specific protein of molecular weight (MW) approximately 55,000 (55K) was found recently by immunoprecipitation in all SV40 virus-transformed mammalian cells, in addition to the SV40 large T antigen (appoximately 94K) and small antigen (approximately 17K), which are the only proteins coded by the 'early half' of the SV40 genome [31].
  • The presence of the E1A protein products as assayed by immunofluorescence does not strictly correlate with the induction of DNA synthesis in microinjected cells in contrast to the SV40 large T-antigen [32].


  1. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Myers, R.M., Rio, D.C., Robbins, A.K., Tjian, R. Cell (1981) [Pubmed]
  2. Intestinal dysplasia induced by simian virus 40 T antigen is independent of p53. Markovics, J.A., Carroll, P.A., Robles, M.T., Pope, H., Coopersmith, C.M., Pipas, J.M. J. Virol. (2005) [Pubmed]
  3. Simian virus 40 large T-antigen, but not small T-antigen, trans-activates the human cytomegalovirus major immediate early promoter. Moens, U., Van Ghelue, M., Kristoffersen, A.K., Johansen, B., Rekvig, O.P., Degré, M., Rollag, H. Virus Genes (2001) [Pubmed]
  4. Role of the amino-terminal domain of simian virus 40 early region in inducing tumors in secretin-expressing cells in transgenic mice. Ratineau, C., Ronco, A., Leiter, A.B. Gastroenterology (2000) [Pubmed]
  5. Requirement for the simian virus 40 small tumor antigen in tumorigenesis in transgenic mice. Choi, Y.W., Lee, I.C., Ross, S.R. Mol. Cell. Biol. (1988) [Pubmed]
  6. Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import. Adam, S.A., Gerace, L. Cell (1991) [Pubmed]
  7. Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. Renfranz, P.J., Cunningham, M.G., McKay, R.D. Cell (1991) [Pubmed]
  8. SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family. Ludlow, J.W., DeCaprio, J.A., Huang, C.M., Lee, W.H., Paucha, E., Livingston, D.M. Cell (1989) [Pubmed]
  9. The mouse type IV c-abl gene product is a nuclear protein, and activation of transforming ability is associated with cytoplasmic localization. Van Etten, R.A., Jackson, P., Baltimore, D. Cell (1989) [Pubmed]
  10. trans-activation of RNA polymerase II and III promoters by SV40 small t antigen. Loeken, M., Bikel, I., Livingston, D.M., Brady, J. Cell (1988) [Pubmed]
  11. Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40 large T antigen to the osteoclast lineage in transgenic mice. Hentunen, T.A., Reddy, S.V., Boyce, B.F., Devlin, R., Park, H.R., Chung, H., Selander, K.S., Dallas, M., Kurihara, N., Galson, D.L., Goldring, S.R., Koop, B.A., Windle, J.J., Roodman, G.D. J. Clin. Invest. (1998) [Pubmed]
  12. Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. al-Ubaidi, M.R., Font, R.L., Quiambao, A.B., Keener, M.J., Liou, G.I., Overbeek, P.A., Baehr, W. J. Cell Biol. (1992) [Pubmed]
  13. Sequence and functional analysis of the positively acting regulatory gene amdR from Aspergillus nidulans. Andrianopoulos, A., Hynes, M.J. Mol. Cell. Biol. (1990) [Pubmed]
  14. The B-domain lysine patch of pRB is required for binding to large T antigen and release of E2F by phosphorylation. Brown, V.D., Gallie, B.L. Mol. Cell. Biol. (2002) [Pubmed]
  15. Association of simian virus 40 T antigen with the nuclear matrix of infected and transformed monkey cells. Covey, L., Choi, Y., Prives, C. Mol. Cell. Biol. (1984) [Pubmed]
  16. Modification of SV40 T antigen by poly ADP-ribosylation. Goldman, N., Brown, M., Khoury, G. Cell (1981) [Pubmed]
  17. Essential contact residues within SV40 large T antigen binding sites I and II identified by alkylation-interference. Jones, K.A., Tjian, R. Cell (1984) [Pubmed]
  18. Inhibition of lens fiber cell morphogenesis by expression of a mutant SV40 large T antigen that binds CREB-binding protein/p300 but not pRb. Chen, Q., Liang, D., Fromm, L.D., Overbeek, P.A. J. Biol. Chem. (2004) [Pubmed]
  19. Structural basis for the cooperative assembly of large T antigen on the origin of replication. Valle, M., Chen, X.S., Donate, L.E., Fanning, E., Carazo, J.M. J. Mol. Biol. (2006) [Pubmed]
  20. Conditional immortalization of normal and dysgenic mouse muscle cells by the SV40 large T antigen under the vimentin promoter control. Pinçon-Raymond, M., Vicart, P., Bois, P., Chassande, O., Romey, G., Varadi, G., Li, Z.L., Lazdunski, M., Rieger, F., Paulin, D. Dev. Biol. (1991) [Pubmed]
  21. Cell adhesion markers are expressed by a stable human endothelial cell line transformed by the SV40 large T antigen under vimentin promoter control. Vicart, P., Testut, P., Schwartz, B., Llorens-Cortes, C., Perdomo, J.J., Paulin, D. J. Cell. Physiol. (1993) [Pubmed]
  22. The SV40 small t antigen is essential for the morphological transformation of human fibroblasts. de Ronde, A., Sol, C.J., van Strien, A., ter Schegget, J., van der Noordaa, J. Virology (1989) [Pubmed]
  23. Characterization of a new simian virus 40 mutant, tsA3900, isolated from deletion mutant tsA1499. Hutchinson, N.I., Chang, L.S., Pater, M.M., Bouck, N., Shenk, T.E., di Mayorca, G. J. Virol. (1985) [Pubmed]
  24. Selection for precise chromosomal targeting of a dominant marker by homologous recombination. Dorin, J.R., Inglis, J.D., Porteous, D.J. Science (1989) [Pubmed]
  25. Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor. Lilyestrom, W., Klein, M.G., Zhang, R., Joachimiak, A., Chen, X.S. Genes Dev. (2006) [Pubmed]
  26. Molecular characterization of a karyophilic, histone-binding protein: cDNA cloning, amino acid sequence and expression of nuclear protein N1/N2 of Xenopus laevis. Kleinschmidt, J.A., Dingwall, C., Maier, G., Franke, W.W. EMBO J. (1986) [Pubmed]
  27. Methylation-induced G(2)/M arrest requires a full complement of the mismatch repair protein hMLH1. Cejka, P., Stojic, L., Mojas, N., Russell, A.M., Heinimann, K., Cannavó, E., di Pietro, M., Marra, G., Jiricny, J. EMBO J. (2003) [Pubmed]
  28. SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen. Bikel, I., Montano, X., Agha, M.E., Brown, M., McCormack, M., Boltax, J., Livingston, D.M. Cell (1987) [Pubmed]
  29. SV40 infection induces telomerase activity in human mesothelial cells. Foddis, R., De Rienzo, A., Broccoli, D., Bocchetta, M., Stekala, E., Rizzo, P., Tosolini, A., Grobelny, J.V., Jhanwar, S.C., Pass, H.I., Testa, J.R., Carbone, M. Oncogene (2002) [Pubmed]
  30. Relationship of oligomerization to enzymatic and DNA-binding properties of the SV40 large T antigen. Bradley, M.K., Griffin, J.D., Livingston, D.M. Cell (1982) [Pubmed]
  31. An embryo protein induced by SV40 virus transformation of mouse cells. Mora, P.T., Chandrasekaran, K., McFarland, V.W. Nature (1980) [Pubmed]
  32. The release of growth arrest by microinjection of adenovirus E1A DNA. Stabel, S., Argos, P., Philipson, L. EMBO J. (1985) [Pubmed]
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