DNA-damage-inducible p53 activity in SV40-transformed cells
| Autor: | Gerhard Brandner, Ralf D. Hess |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Gene Expression Regulation Viral Cancer Research SV40 large T antigen Tumor suppressor gene DNA damage Antigens Polyomavirus Transforming Mitomycin Simian virus 40 Biology Mice chemistry.chemical_compound Antigen Cyclins Gene expression Genetics Animals Molecular Biology Cell Line Transformed Mice Inbred BALB C Mitomycin C Cell Transformation Viral Genes p53 Virology Molecular biology Mice Inbred C57BL chemistry Cell culture Tumor Suppressor Protein p53 DNA DNA Damage |
| Zdroj: | Oncogene. 15:2501-2504 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1201404 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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