Figure 6

Working model of p53 action to IGFBP-3 promoter. In normal cells, IGFBP-3 is induced by such as growth hormone and IGFs, and steady level of expression is observed in some cells. As the deletion of p53 binding sites enhances the expression of IGFBP-3, the binding of negative regulators is expected (Fig. 6A). In apoptotic cells, p53 tetramers at high level of expression bind to upstream binding sites. These tetramers recruit the p300 complex to its binding site, and a p53 dependent high level of expression is observed (Fig. 6B). In tumor cells, deletions, mutations, methylations of p53 binding sites, or mutations of p53 such as p53mt135, disturb the binding of p53 tetramers to its binding sites, and this prevents the binding of p300. As a result, the expression of IGFBP-3 is suppressed in tumor cells.