title: Response of heat shock element within the human HSP70 promoter to mutated p53 genes.
abstract: Recent studies have demonstrated that mutation of the p53 gene caused a gain of new functions such as transforming activation, binding to heat shock cognate protein 70 and/or transactivation of a variety of promoters. In the course of seeking the biochemical basis for the gain of these functions, we have noticed the correlation between transforming activity of different mutated p53 genes and their transactivational activity on the human heat shock protein 70 promoter. Analysis of 5' deletion constructs of the heat shock protein 70 promoter showed that some specific elements within the heat shock domain containing two heat shock elements (HSEs) could respond to mutant p53 species but not basic promoter elements such as the TATA box, CCAAT box, and GC box. Subsequently, we identified the HSE as a responsive element using reporter constructs of minimal promoter containing synthetic proximal HSE, distal HSE, or GC/CCAAT box. Further analysis using in vitro mutagenesis of HSE suggests that HSE with heat shock factor binding ability is required for transactivation of the heat shock protein 70 promoter by mutated p53 genes.
authors.affiliation: Department of Molecular Cellular Oncology and Microbiology, Faculty of Dentistry, Tokyo Medical and Dental University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsutsumi-Ishii
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: F
authors.initials: F
authors.lastname: Hanaoka
authors.forename: N
authors.initials: N
authors.lastname: Tsuchida
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D018840:HSP70 Heat-Shock Proteins