The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs

Many in vitro and in vivo evidence have shown that the status of p53 is a key determinant in the response of tumor cells to anticancer treatment. Here we provide evidence that peptide-mediated targeting of the protein complex mutantp53/p73 enhances the response of mutant p53 tumor cells to commonly...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2008-11, Vol.7 (21), p.3440-3447
Main Authors: Di Agostino, Silvia, Cortese, Giancarlo, Monti, Olimpia, Dell'Orso, Stefania, Sacchi, Ada, Eisenstein, Miriam, Citro, Gennaro, Strano, Sabrina, Blandino, Giovanni
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Line, Tumor
Cisplatin - pharmacology
Cycle
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Doxorubicin - pharmacology
Drug Screening Assays, Antitumor
Humans
Landes
Models, Biological
Multiprotein Complexes - metabolism
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Organogenesis
Peptides - pharmacology
Promoter Regions, Genetic
Protein Binding - drug effects
Proteins
Transcription, Genetic - drug effects
Transduction, Genetic
Tumor Protein p73
Tumor Suppressor Protein p53 - metabolism
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
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Summary:Many in vitro and in vivo evidence have shown that the status of p53 is a key determinant in the response of tumor cells to anticancer treatment. Here we provide evidence that peptide-mediated targeting of the protein complex mutantp53/p73 enhances the response of mutant p53 tumor cells to commonly used anticancer drugs. Indeed, we show that the disruption of the protein complex mutantp53/p73 and the consequent restoration of p73 transcriptional effects, through the activity of short interfering peptides, render mutant p53 cells more prone to the killing of adriamycin and cisplatin. Of note, the activity of the short interfering peptides is mutant p53 specific and causes no effects on wt-p53 and p53 null cells. Our findings highlight the protein complex mutantp53/p73 as a molecular target, whose successful overriding through the selective activity of small interfering peptides, might contribute to the optimization of mutant p53 tumor treatments.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.7.21.6995