RESPONSE OF HEAT-SHOCK ELEMENT WITHIN THE HUMAN HSP70 PROMOTER TO MUTATED P53 GENES

Recent studies have demonstrated that mutation of the p53 gene caused a gain of new functions such as transforming activation, binding to he at shock cognate protein 70 and/or transactivation of a variety of pro moters. 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 a ctivity on the human heat shock protein 70 promoter. Analysis of 5' de letion constructs of the heat shock protein 70 promoter showed that so me specific elements within the heat shock domain containing two heat shock elements (HSEs) could respond to mutant p53 species but not basi c promoter elements such as the TATA box, CCAAT box, and GC box. Subse quently, we identified the HSE as a responsive element using reporter constructs of minimal promoter containing synthetic proximal HSE, dist al HSE, or GC/CCAAT box. Further analysis using in vitro mutagenesis o f HSE suggests that HSE with heat shock factor binding ability is requ ired for transactivation of the heat shock protein 70 promoter by muta ted p53 genes.