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Mol. Cell. Biol., Aug 1995, 4489-4496, Vol 15, No. 8
X Sun, H Shimizu and K Yamamoto
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.
Copyright © 1995, American Society for Microbiology
Identification of a novel p53 promoter element involved in genotoxic stress-inducible p53 gene expression
Department of Molecular Pathology, Kanazawa University, Ishikawa, Japan.
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