RESTORATION OF THE GROWTH SUPPRESSION FUNCTION OF MUTANT P53 BY A SYNTHETIC PEPTIDE DERIVED FROM THE P53 C-TERMINAL DOMAIN

We demonstrate here that synthetic 22-mer peptide 46, corresponding to the carboxy-terminal amino acid residues 361-382 of p53, can activate specific DNA binding of wild-type p53 in vitro and can restore the tr anscriptional transactivating function of at least some mutant p53 pro teins in living cells. Introduction of peptide 46 in Saos-2 cells carr ying a Tet-regulatable His-273 mutant p53 construct caused growth inhi bition and apoptosis in the presence of mutant p53 but not in its abse nce, confirming that the effect of the peptide is mediated by reactiva tion of mutant p53. Moreover, peptide 46 caused apoptosis in mutant as well as wild-type p53-carrying human tumor cell lines of different or igin, whereas p53 null tumor cells were not affected. These findings r aise possibilities for developing drugs that restore the tumor suppres sor function of mutant p53 proteins, thus selectively eliminating tumo r cells.