Peptide 46, a synthetic 22-mer peptide derived from the p53 C-terminal domain, can restore the growth suppressor function of mutant p53 proteins in human tumor cells. The sequence of peptide 46, which corresponds to residues 361 to 382 in the p53 C terminus, is (in one-letter code) GSRAHSSHLKSKKGQSTSRHKK[1]. Teptide 46, the only C-terminal peptide that can activate the specific DNA binding of p53, changed the mobility of the core domain, whereas the other C-terminal peptides did not. Conversely, the mobility of the C-terminal domain protein was shifted upon incubation with the core domain protein.