Description

The anticancer peptide PNC-27, which contains an HDM-2-binding domain corresponding to residues 12-26 of

p53 and a transmembrane-penetrating domain, has been found to kill cancer cells (but not normal cells) by

inducing membranolysis. We find that our previously determined 3D structure of the p53 residues of PNC-27 is

directly superimposable on the structure for the same residues bound to HDM-2, suggesting that the peptide may

target HDM-2 in the membranes of cancer cells.

Application&Function

We now find significant levels of HDM-2 in the membranes of a varietyof cancer cells but not in the membranes of

several untransformed cell lines. In colocalization experiments, we find that PNC-27 binds to cell membrane-bound

HDM-2. We further transfected a plasmid expressing full-length HDM-2 with a membrane-localization signal into

untransformed MCF-10-2A cells not susceptible to PNC-27 and found that these cells expressing full-length HDM-2

on their cell surface became susceptible to PNC-27. We conclude that PNC-27 targets HDM-2 in the membranes of

cancer cells, allowing it to induce membranolysis of these cells selectively.