DNA-damage-inducible p53 activity in SV40-transformed cells.
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.
Hess
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RD
Department of Virology, Institute for Medical Microbiology & Hygiene, University of Freiburg, Germany.
Brandner
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G
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000235:genetics; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004249:DNA Damage; D015967:Gene Expression Regulation, Viral; D016158:Genes, p53; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016685:Mitomycin / Q000494:pharmacology; D013539:Simian virus 40 / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000952:Antigens, Polyomavirus Transforming; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin