WILD-TYPE BUT NOT MUTANT P53 ACTIVATES THE HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR PROMOTER

p53 transactivates the expression of a variety of genes by binding to specific DNA sequences within the promoter. We have investigated the a bility of wild-type p53 and a non-DNA binding p53 mutant to activate t he hepatocyte growth factor/scatter factor (HGF/SF) promoter using chl oramphenicol acetyltransferase reporter constructs. We also used delet ion sequences of the HGF/SF promoter to identify which regions, if any , were responsible for p53 binding. Our results show that wild-type bu t not mutant p53 activates the HGF/SF promoter when using -3000 and -7 55 bp upstream of the HGF/SF gene. This activation is lost when promot er sequences covering -365 and -239 bp are used. Analysis of the DNA s equence between -365 and -755 bp shows one putative p53 half-Site with 80% homology to the consensus sequence and another half-site 3 bases downstream of this with 100% homology to the consensus sequence. In co ntrast to previously identified p53 binding DNA sequences, the downstr eam half-site is inverted. We propose that the HGF/SF promoter can be activated by wild-type p53 in vivo and that this could be as a result of a novel form of sequence-specific DNA binding.