Transcriptional repression of the human p53 gene by cobalt chloride mimicking hypoxia.
The switch to an angiogenic phenotype is known to be a fundamental determinant of neoplastic growth and tumor progression. We herein report that the transcription of the human p53 gene was repressed by treatment with a hypoxia-mimicking concentration of cobalt chloride and alone by hypoxia-inducible factor 1alpha. Analyses of serial deletions, site-directed mutageneses and heterologous promoter systems showed that the site responsible for the repression by both factors was the E-box element in the promoter of the p53 gene. These results alongside previous data suggest that the loss of p53 including the transcriptional repression may play an important role in the angiogenic switch during tumorigenesis.
Lee
S G
SG
School of Biological Sciences, Seoul National University, 151-742, Seoul, South Korea.
Lee
H
H
Rho
H M
HM
D015687:Cell Hypoxia / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024721:E-Box Elements; D016259:Genes, myc; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D003035:Cobalt; C018021:cobaltous chloride