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Mol Cell Biol. Dec 1987; 7(12): 4453–4463.
PMCID: PMC368129

Modulation of p53 protein expression during cellular transformation with simian virus 40.

Abstract

We analyzed the relation of metabolic stabilization of the p53 protein during cellular transformation by simian virus 40 (SV40) to (i) expression of the transformed phenotype and (ii) expression of the large tumor antigen (large T). Analysis of SV40-tsA28-mutant-transformed rat cells (tsA28.3 cells) showed that both p53 complexed to large T and free p53 (W. Deppert and M. Haug, Mol. Cell. Biol. 6:2233-2240, 1986) were metabolically stable when the cells were cultured at 32 degrees C and expressed large T and the transformed phenotype. At the nonpermissive temperature (39 degrees C), large-T expression is shut off in these cells and they revert to the normal phenotype. In such cells, p53 was metabolically unstable, like p53 in untransformed cells. To determine whether metabolic stabilization of p53 is directly controlled by large T, we next analyzed the metabolic stability of complexed and free p53 in SV40 abortively infected normal BALB/c mouse 3T3 cells. We found that neither p53 in complex with large T nor free p53 was metabolically stable. However, both forms of p53 were stabilized in SV40-transformed cells which had been developed in parallel from SV40 abortively infected cultures. Our results indicate that neither formation of a complex of p53 with large T nor large-T expression as such is sufficient for a significant metabolic stabilization of p53. Therefore, we suggest that metabolic stabilization of p53 during cellular transformation with SV40 is mediated by a cellular process and probably is the consequence of the large-T-induced transformed phenotype.

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Selected References

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  • Chandrasekaran K, McFarland VW, Simmons DT, Dziadek M, Gurney EG, Mora PT. Quantitation and characterization of a species-specific and embryo stage-dependent 55-kilodalton phosphoprotein also present in cells transformed by simian virus 40. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6953–6957. [PMC free article] [PubMed]
  • Crawford L. The 53,000-dalton cellular protein and its role in transformation. Int Rev Exp Pathol. 1983;25:1–50. [PubMed]
  • Deppert W. SV40 T-antigen-related surface antigen: correlated expression with nuclear T-antigen in cells transformed by an SV40 A-gene mutant. Virology. 1980 Jul 30;104(2):497–501. [PubMed]
  • Deppert W, Haug M. Evidence for free and metabolically stable p53 protein in nuclear subfractions of simian virus 40-transformed cells. Mol Cell Biol. 1986 Jun;6(6):2233–2240. [PMC free article] [PubMed]
  • Eliyahu D, Raz A, Gruss P, Givol D, Oren M. Participation of p53 cellular tumour antigen in transformation of normal embryonic cells. Nature. 1984 Dec 13;312(5995):646–649. [PubMed]
  • Gambke C, Deppert W. Late nonstructural 100,000- and 33,000-dalton proteins of adenovirus type 2. I. Subcellular localization during the course of infection. J Virol. 1981 Nov;40(2):585–593. [PMC free article] [PubMed]
  • Gronostajski RM, Goldberg AL, Pardee AB. Energy requirement for degradation of tumor-associated protein p53. Mol Cell Biol. 1984 Mar;4(3):442–448. [PMC free article] [PubMed]
  • Gurney EG, Harrison RO, Fenno J. Monoclonal antibodies against simian virus 40 T antigens: evidence for distinct sublcasses of large T antigen and for similarities among nonviral T antigens. J Virol. 1980 Jun;34(3):752–763. [PMC free article] [PubMed]
  • Gurney EG, Tamowski S, Deppert W. Antigenic binding sites of monoclonal antibodies specific for simian virus 40 large T antigen. J Virol. 1986 Mar;57(3):1168–1172. [PMC free article] [PubMed]
  • Hinzpeter M, Deppert W. Analysis of biological and biochemical parameters for chromatin and nuclear matrix association of SV40 large T antigen in transformed cells. Oncogene. 1987 May;1(2):119–129. [PubMed]
  • Jenkins JR, Rudge K, Chumakov P, Currie GA. The cellular oncogene p53 can be activated by mutagenesis. Nature. 317(6040):816–818. [PubMed]
  • Jenkins JR, Rudge K, Currie GA. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 1984 Dec 13;312(5995):651–654. [PubMed]
  • Kriegler M, Perez CF, Hardy C, Botchan M. Transformation mediated by the SV40 T antigens: separation of the overlapping SV40 early genes with a retroviral vector. Cell. 1984 Sep;38(2):483–491. [PubMed]
  • Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. [PubMed]
  • Linzer DI, Levine AJ. 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. [PubMed]
  • Linzer DI, Maltzman W, Levine AJ. The SV40 A gene product is required for the production of a 54,000 MW cellular tumor antigen. Virology. 1979 Oct 30;98(2):308–318. [PubMed]
  • Martin RG. The transformation of cell growth and transmogrification of DNA synthesis by simian virus 40. Adv Cancer Res. 1981;34:1–68. [PubMed]
  • Matlashewski GJ, Tuck S, Pim D, Lamb P, Schneider J, Crawford LV. Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol. 1987 Feb;7(2):961–963. [PMC free article] [PubMed]
  • Michalovitz D, Eliyahu D, Oren M. Overproduction of protein p53 contributes to simian virus 40-mediated transformation. Mol Cell Biol. 1986 Oct;6(10):3531–3536. [PMC free article] [PubMed]
  • Oren M. The p53 cellular tumor antigen: gene structure, expression and protein properties. Biochim Biophys Acta. 1985 Nov 12;823(1):67–78. [PubMed]
  • Oren M, Maltzman W, Levine AJ. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. [PMC free article] [PubMed]
  • Oren M, Reich NC, Levine AJ. Regulation of the cellular p53 tumor antigen in teratocarcinoma cells and their differentiated progeny. Mol Cell Biol. 1982 Apr;2(4):443–449. [PMC free article] [PubMed]
  • Osborn M, Weber K. Simian virus 40 gene A function and maintenance of transformation. J Virol. 1975 Mar;15(3):636–644. [PMC free article] [PubMed]
  • Parada LF, Land H, Weinberg RA, Wolf D, Rotter V. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature. 1984 Dec 13;312(5995):649–651. [PubMed]
  • Reich NC, Oren M, Levine AJ. Two distinct mechanisms regulate the levels of a cellular tumor antigen, p53. Mol Cell Biol. 1983 Dec;3(12):2143–2150. [PMC free article] [PubMed]
  • Risser R, Pollack R. A nonselective analysis of SV40 transformation of mouse 3T3 cells. Virology. 1974 Jun;59(2):477–489. [PubMed]
  • Rotter V. p53, a transformation-related cellular-encoded protein, can be used as a biochemical marker for the detection of primary mouse tumor cells. Proc Natl Acad Sci U S A. 1983 May;80(9):2613–2617. [PMC free article] [PubMed]
  • Rotter V, Abutbul H, Ben-Ze'ev A. P53 transformation-related protein accumulates in the nucleus of transformed fibroblasts in association with the chromatin and is found in the cytoplasm of non-transformed fibroblasts. EMBO J. 1983;2(7):1041–1047. [PMC free article] [PubMed]
  • Rotter V, Wolf D. Biological and molecular analysis of p53 cellular-encoded tumor antigen. Adv Cancer Res. 1985;43:113–141. [PubMed]
  • Rovinski B, Munroe D, Peacock J, Mowat M, Bernstein A, Benchimol S. Deletion of 5'-coding sequences of the cellular p53 gene in mouse erythroleukemia: a novel mechanism of oncogene regulation. Mol Cell Biol. 1987 Feb;7(2):847–853. [PMC free article] [PubMed]
  • Samad A, Anderson CW, Carroll RB. Mapping of phosphomonoester and apparent phosphodiester bonds of the oncogene product p53 from simian virus 40-transformed 3T3 cells. Proc Natl Acad Sci U S A. 1986 Feb;83(4):897–901. [PMC free article] [PubMed]
  • Sarnow P, Ho YS, Williams J, Levine AJ. Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell. 1982 Feb;28(2):387–394. [PubMed]
  • Staufenbiel M, Deppert W. Different structural systems of the nucleus are targets for SV40 large T antigen. Cell. 1983 May;33(1):173–181. [PubMed]
  • Staufenbiel M, Deppert W. Preparation of nuclear matrices from cultured cells: subfractionation of nuclei in situ. J Cell Biol. 1984 May;98(5):1886–1894. [PMC free article] [PubMed]
  • Zantema A, Schrier PI, Davis-Olivier A, van Laar T, Vaessen RT, van der EB AJ. Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells. Mol Cell Biol. 1985 Nov;5(11):3084–3091. [PMC free article] [PubMed]

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