Abstract
Metabolic stabilization of the tumor suppressor p53 is a key event in cellular transformation by simian virus 40 (SV40). Expression of the SV40 large tumor antigen (large T) is necessary but not sufficient for this process, as metabolic stabilization of p53 complexed to large T in abortively SV40-infected cells strictly depends on the cellular systems analyzed (F. Tiemann and W. Deppert, J. Virol. 68:2869-2878, 1994). Comparative analyses of various cells differing in metabolic stabilization of p53 upon abortive infection with SV40 revealed that metabolic stabilization of p53 closely correlated with expression of the SV40 small t antigen (small t) in these cells: 3T3 cells do not express small t and do not stabilize p53 upon infection with wild-type SV40. However, ectopic expression of small t in 3T3 cells provided these cells with the capacity to stabilize p53 upon SV40 infection. Conversely, precrisis mouse embryo cells express small t and mediate metabolic stabilization of p53 upon infection with wild-type SV40. Infection of these cells with an SV40 small-t deletion mutant did not lead to metabolic stabilization of p53. Small-t expression and metabolic stabilization of p53 correlated with an enhanced transformation efficiency by SV40, supporting the conclusion that at least part of the documented helper effect of small t in SV40 transformation is its ability to promote metabolic stabilization of p53 complexed to large T.
Full Text
The Full Text of this article is available as a PDF (573.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aaronson S. A., Todaro G. J. Development of 3T3-like lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40. J Cell Physiol. 1968 Oct;72(2):141–148. doi: 10.1002/jcp.1040720208. [DOI] [PubMed] [Google Scholar]
- Bikel I., Montano X., Agha M. E., Brown M., McCormack M., Boltax J., Livingston D. M. SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen. Cell. 1987 Jan 30;48(2):321–330. doi: 10.1016/0092-8674(87)90435-1. [DOI] [PubMed] [Google Scholar]
- Caron de Fromentel C., Soussi T. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer. 1992 Jan;4(1):1–15. doi: 10.1002/gcc.2870040102. [DOI] [PubMed] [Google Scholar]
- Chang L. S., Pater M. M., Hutchinson N. I., di Mayorca G. Transformation by purified early genes of simian virus 40. Virology. 1984 Mar;133(2):341–353. doi: 10.1016/0042-6822(84)90400-8. [DOI] [PubMed] [Google Scholar]
- Crawford L. The 53,000-dalton cellular protein and its role in transformation. Int Rev Exp Pathol. 1983;25:1–50. [PubMed] [Google Scholar]
- Deppert W., Haug M., Steinmayer T. Modulation of p53 protein expression during cellular transformation with simian virus 40. Mol Cell Biol. 1987 Dec;7(12):4453–4463. doi: 10.1128/mcb.7.12.4453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deppert W., Steinmayer T., Richter W. Cooperation of SV40 large T antigen and the cellular protein p53 in maintenance of cell transformation. Oncogene. 1989 Sep;4(9):1103–1110. [PubMed] [Google Scholar]
- Deppert W. The yin and yang of p53 in cellular proliferation. Semin Cancer Biol. 1994 Jun;5(3):187–202. [PubMed] [Google Scholar]
- Farmer G., Bargonetti J., Zhu H., Friedman P., Prywes R., Prives C. Wild-type p53 activates transcription in vitro. Nature. 1992 Jul 2;358(6381):83–86. doi: 10.1038/358083a0. [DOI] [PubMed] [Google Scholar]
- Feunteun J., Kress M., Gardes M., Monier R. Viable deletion mutants in the simian virus 40 early region. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4455–4459. doi: 10.1073/pnas.75.9.4455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freeman A. E., Igel H. J., Price P. J. I. In vitrol transformation of rat embryo cells: correlations with the known tumorigenic activities of chemicals in rodents. In Vitro. 1975 Mar-Apr;11(2):107–116. doi: 10.1007/BF02624083. [DOI] [PubMed] [Google Scholar]
- Gannon J. V., Greaves R., Iggo R., Lane D. P. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J. 1990 May;9(5):1595–1602. doi: 10.1002/j.1460-2075.1990.tb08279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
- Harlow E., Crawford L. V., Pim D. C., Williamson N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol. 1981 Sep;39(3):861–869. doi: 10.1128/jvi.39.3.861-869.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harlow E., Pim D. C., Crawford L. V. Complex of simian virus 40 large-T antigen and host 53,000-molecular-weight protein in monkey cells. J Virol. 1981 Feb;37(2):564–573. doi: 10.1128/jvi.37.2.564-573.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harris C. C., Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993 Oct 28;329(18):1318–1327. doi: 10.1056/NEJM199310283291807. [DOI] [PubMed] [Google Scholar]
- Harris C. C. p53: at the crossroads of molecular carcinogenesis and risk assessment. Science. 1993 Dec 24;262(5142):1980–1981. doi: 10.1126/science.8266092. [DOI] [PubMed] [Google Scholar]
- Harvey D. M., Levine A. J. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev. 1991 Dec;5(12B):2375–2385. doi: 10.1101/gad.5.12b.2375. [DOI] [PubMed] [Google Scholar]
- Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
- Kastan M. B., Onyekwere O., Sidransky D., Vogelstein B., Craig R. W. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991 Dec 1;51(23 Pt 1):6304–6311. [PubMed] [Google Scholar]
- Lane D. P. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15–16. doi: 10.1038/358015a0. [DOI] [PubMed] [Google Scholar]
- Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
- Lane D. P. Worrying about p53. Curr Biol. 1992 Nov;2(11):581–583. doi: 10.1016/0960-9822(92)90154-3. [DOI] [PubMed] [Google Scholar]
- Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
- Livingstone L. R., White A., Sprouse J., Livanos E., Jacks T., Tlsty T. D. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell. 1992 Sep 18;70(6):923–935. doi: 10.1016/0092-8674(92)90243-6. [DOI] [PubMed] [Google Scholar]
- Loeken M., Bikel I., Livingston D. M., Brady J. trans-activation of RNA polymerase II and III promoters by SV40 small t antigen. Cell. 1988 Dec 23;55(6):1171–1177. doi: 10.1016/0092-8674(88)90261-9. [DOI] [PubMed] [Google Scholar]
- Martin R. G., Setlow V. P., Edwards C. A., Vembu D. The roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells. Cell. 1979 Jul;17(3):635–643. doi: 10.1016/0092-8674(79)90271-x. [DOI] [PubMed] [Google Scholar]
- Montano X., Lane D. P. Monoclonal antibody to simian virus 40 small t. J Virol. 1984 Sep;51(3):760–767. doi: 10.1128/jvi.51.3.760-767.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montano X., Millikan R., Milhaven J. M., Newsom D. A., Ludlow J. W., Arthur A. K., Fanning E., Bikel I., Livingston D. M. Simian virus 40 small tumor antigen and an amino-terminal domain of large tumor antigen share a common transforming function. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7448–7452. doi: 10.1073/pnas.87.19.7448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mungre S., Enderle K., Turk B., Porrás A., Wu Y. Q., Mumby M. C., Rundell K. Mutations which affect the inhibition of protein phosphatase 2A by simian virus 40 small-t antigen in vitro decrease viral transformation. J Virol. 1994 Mar;68(3):1675–1681. doi: 10.1128/jvi.68.3.1675-1681.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patschinsky T., Deppert W. Phosphorylation of p53 in primary, immortalised and transformed Balb/c mouse cells. Oncogene. 1990 Jul;5(7):1071–1076. [PubMed] [Google Scholar]
- Prives C., Bargonetti J., Friedman P. N., Manfredi J. J., Wang E. H. Functional consequences of the interactions of the p53 tumor suppressor protein and SV40 large tumor antigen. Cold Spring Harb Symp Quant Biol. 1991;56:227–235. doi: 10.1101/sqb.1991.056.01.028. [DOI] [PubMed] [Google Scholar]
- Rassoulzadegan M., Gaudray P., Canning M., Trejo-Avila L., Cuzin F. Two polyoma virus gene functions involved in the expression of the transformed phenotype in FR 3T3 rat cells. I. Localization of a transformation maintenance function in the proximal half of the large T coding region. Virology. 1981 Oct 30;114(2):489–500. doi: 10.1016/0042-6822(81)90228-2. [DOI] [PubMed] [Google Scholar]
- Risser R., Pollack R. A nonselective analysis of SV40 transformation of mouse 3T3 cells. Virology. 1974 Jun;59(2):477–489. doi: 10.1016/0042-6822(74)90457-7. [DOI] [PubMed] [Google Scholar]
- Rubin H., Figge J., Bladon M. T., Chen L. B., Ellman M., Bikel I., Farrell M., Livingston D. M. Role of small t antigen in the acute transforming activity of SV40. Cell. 1982 Sep;30(2):469–480. doi: 10.1016/0092-8674(82)90244-6. [DOI] [PubMed] [Google Scholar]
- Rubin H., Xu K. Evidence for the progressive and adaptive nature of spontaneous transformation in the NIH 3T3 cell line. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1860–1864. doi: 10.1073/pnas.86.6.1860. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scheffner M., Werness B. A., Huibregtse J. M., Levine A. J., Howley P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990 Dec 21;63(6):1129–1136. doi: 10.1016/0092-8674(90)90409-8. [DOI] [PubMed] [Google Scholar]
- Su L., Hershberger R. J., Weissman I. L. LYAR, a novel nucleolar protein with zinc finger DNA-binding motifs, is involved in cell growth regulation. Genes Dev. 1993 May;7(5):735–748. doi: 10.1101/gad.7.5.735. [DOI] [PubMed] [Google Scholar]
- Sugden B., Marsh K., Yates J. A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus. Mol Cell Biol. 1985 Feb;5(2):410–413. doi: 10.1128/mcb.5.2.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tiemann F., Deppert W. Immortalization of BALB/c mouse embryo fibroblasts alters SV40 large T-antigen interactions with the tumor suppressor p53 and results in a reduced SV40 transformation-efficiency. Oncogene. 1994 Jul;9(7):1907–1915. [PubMed] [Google Scholar]
- Tiemann F., Deppert W. Stabilization of the tumor suppressor p53 during cellular transformation by simian virus 40: influence of viral and cellular factors and biological consequences. J Virol. 1994 May;68(5):2869–2878. doi: 10.1128/jvi.68.5.2869-2878.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang S. I., Lickteig R. L., Estes R., Rundell K., Walter G., Mumby M. C. Control of protein phosphatase 2A by simian virus 40 small-t antigen. Mol Cell Biol. 1991 Apr;11(4):1988–1995. doi: 10.1128/mcb.11.4.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yin Y., Tainsky M. A., Bischoff F. Z., Strong L. C., Wahl G. M. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell. 1992 Sep 18;70(6):937–948. doi: 10.1016/0092-8674(92)90244-7. [DOI] [PubMed] [Google Scholar]
- Zerrahn J., Deppert W. Analysis of simian virus 40 small t antigen-induced progression of rat F111 cells minimally transformed by large T antigen. J Virol. 1993 Mar;67(3):1555–1563. doi: 10.1128/jvi.67.3.1555-1563.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zerrahn J., Knippschild U., Winkler T., Deppert W. Independent expression of the transforming amino-terminal domain of SV40 large I antigen from an alternatively spliced third SV40 early mRNA. EMBO J. 1993 Dec;12(12):4739–4746. doi: 10.1002/j.1460-2075.1993.tb06162.x. [DOI] [PMC free article] [PubMed] [Google Scholar]