Affiliation:
1. Department of Molecular Pathology, Kanazawa University, Ishikawa, Japan.
Abstract
p53 is recruited in response to DNA-damaging genotoxic stress and plays an important role in maintaining the integrity of the genome. We show that exposure of cells to various genotoxic agents, including anticancer drugs such as mitomycin and 5-fluorouracil, results in an increase in p53 mRNA levels and in p53 promoter activation, indicating that the p53 genotoxic stress response is partly regulated at the transcriptional level. The results of the p53 promoter analysis show that a novel p53 promoter element, termed a p53 core promoter element (from -70 to -46), is essential for basal p53 promoter activity and promoter activation induced by genotoxic agents such as anticancer drugs and UV. Although a kappa B motif partially overlaps with this element and those genotoxic agents activate NF-kappa B, it does not play a major role in p53 genotoxic stress response: NF-kappa B p65 expression did not induce significant p53 promoter activation, and NF-kappa B inhibitors (N-acetyl cysteine and I kappa B alpha) did not inhibit genotoxic stress-inducible p53 promoter activation. Finally, we characterized nuclear factors, the binding of which to the p53 core promoter element is essential for basal p53 promoter activity and p53 promoter activation induced by genotoxic agents.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference55 articles.
1. Heat shock-induced interactions of heat shock transcription factor and the human hsp70 promoter examined by in vivo footprinting;Abravaya K.;Mol. Cell. Biol.,1991
2. Baldwin A. S. Jr. 1988. Methylation interference assay for analysis of DNAprotein interactions p. 12.3. In K. Janssen (ed.) Current protocols in molecular biology. Wiley Interscience New York.
3. The I~B proteins: multifunctional regulators of Rel/NF-~B transcription factors;Beg A. A.;Genes Dev.,1993
4. c-myc gene is transcribed at high rate in G0-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors;Blanchard J.;Nature (London),1985
5. Improved methodology for isolation of intact and highly active ribonucleic acid;Cathala G.;DNA,1983
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