Journal article
Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes
Proceedings of the National Academy of Sciences - PNAS, v 107(5), pp 1918-1923
11 Jan 2010
PMID: 20080680
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes
- Creators
- Ehsan Sarafraz-Yazdi - SUNY Downstate Health Sciences UniversityWilbur B. Bowne - SUNY Downstate Health Sciences UniversityVictor Adler - VA Medical CenterKelley A. Sookraj - SUNY Downstate Health Sciences UniversityVernon Wu - SUNY Downstate Health Sciences UniversityVadim Shteyler - SUNY Downstate Health Sciences UniversityHunaiz Patel - SUNY Downstate Health Sciences UniversityWilliam Oxbury - SUNY Downstate Health Sciences UniversityPaul Brandt-Rauf - University of Illinois Urbana-ChampaignMichael E. Zenilman - SUNY Downstate Health Sciences UniversityJosef Michl - SUNY Downstate Health Sciences UniversityMatthew R. Pincus - SUNY Downstate Health Sciences University
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 107(5), pp 1918-1923
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000274296300023
- Scopus ID
- 2-s2.0-76649141217
- Other Identifier
- 991019323773404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology