Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes.

Abstract:

: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. We now find significant levels of HDM-2 in the membranes of a variety of 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.

authors

Sarafraz-Yazdi E,Bowne WB,Adler V,Sookraj KA,Wu V,Shteyler V,Patel H,Oxbury W,Brandt-Rauf P,Zenilman ME,Michl J,Pincus MR

doi

10.1073/pnas.0909364107

subject

Has Abstract

pub_date

2010-02-02 00:00:00

pages

1918-23

issue

5

eissn

0027-8424

issn

1091-6490

pii

0909364107

journal_volume

107

pub_type

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