DNA-damage-inducible p53 activity in SV40-transformed cells (original) (raw)

Oncogene volume 15, pages 2501–2504 (1997)Cite this article

Abstract

The biological state of the tumour suppressor proteins Rb and p53 is altered in papillomavirus- and SV40-transformed cells, due to interaction with the DNA tumour virus oncogene proteins E6/E7 and the tumour (T) antigen. Thus, the DNA damage response function of p53, a crucial feature of the tumour suppressor p53, might be considered as inactive. To investigate this subject, C57SV and VLM, two SV40-transformed murine cell lines enharboring constitutively high nuclear p53 and SV40 large T antigen levels, were treated with mitomycin C. Mitomycin C is known for its activity to elicit DNA damage, followed by nuclear accumulation of biologically active p53. Surprisingly, the nuclear p53 level significantly increased in mitomycin-C-treated C57SV cells and to a lesser degree in VLM cells. In addition, expression of p21WAF1 protein was induced in C57SV and VLM cells. This indicates a possible DNA-damage-elicited p53 activation. Finally, nuclear extracts of mitomycin-C-treated C57SV and VLM cells, but not of untreated cells, exhibited PAb421-enhanced specific DNA-binding activity of p53, as proven by gel shift analysis. Thus, DNA damage induced essential biological functions typical for wild-type p53 in the SV40-transformed cell lines examined so far.

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  1. Department of Virology, Institute for Medical Microbiology & Hygiene, University of Freiburg, POB 820, Freiburg, D 79008, Germany
    Ralf D Hess & Gerhard Brandner

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  1. Ralf D Hess
  2. Gerhard Brandner

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Hess, R., Brandner, G. DNA-damage-inducible p53 activity in SV40-transformed cells.Oncogene 15, 2501–2504 (1997). https://doi.org/10.1038/sj.onc.1201404

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