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PNC-27, an anticancer peptide, containing an HDM-2 binding domain corresponding to p53 residues 12-26 and a transmembrane penetrating domain, has been found to kill cancer cells but not normal cells by inducing membrane lysis. The 3D structure of the p53 residue of PNC-27 directly overlaps the structure of the same residue that binds HDM-2, suggesting that this peptide may target HDM-2 in the cell membrane. The researchers found significant levels of HDM-2 in the cell membranes of a variety of cancer cells but not in some untransformed cell lines. In colocalization experiments, PNC-27 bound to cell membrane-bound HDM-2. The researchers used a membrane localization signal to transfect a plasmid expressing full-length HDM-2 into PNC-27-insensitive untransformed MCF-10-2A cells and found that these cells expressed full-length HDM-2 on their cell surface. cells versus PNC-27. We concluded that PNC-27 targets HDM-2 in cancer cell membranes, allowing it to selectively induce membrane lysis in these cells.