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

Silvia Di Agostino, Giancarlo Cortese, Olimpia Monti, Stefania Dell'Orso, Ada Sacchi, Miriam Eisenstein, Gennaro Citro, Sabrina Strano, Giovanni Blandino

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3440-3447
Number of pages8
JournalCell Cycle
Volume7
Issue number21
Publication statusPublished - Nov 1 2008

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Peptides
Pharmaceutical Preparations
Neoplasms
Proteins
Null Lymphocytes
Protein Transport
Doxorubicin
Cisplatin
In Vitro Techniques

Keywords

  • Apoptosis
  • DNA damage
  • Mutant p53
  • p73
  • Short peptides

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Di Agostino, S., Cortese, G., Monti, O., Dell'Orso, S., Sacchi, A., Eisenstein, M., ... Blandino, G. (2008). The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs. Cell Cycle, 7(21), 3440-3447.

The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs. / Di Agostino, Silvia; Cortese, Giancarlo; Monti, Olimpia; Dell'Orso, Stefania; Sacchi, Ada; Eisenstein, Miriam; Citro, Gennaro; Strano, Sabrina; Blandino, Giovanni.

In: Cell Cycle, Vol. 7, No. 21, 01.11.2008, p. 3440-3447.

Research output: Contribution to journalArticle

Di Agostino, S, Cortese, G, Monti, O, Dell'Orso, S, Sacchi, A, Eisenstein, M, Citro, G, Strano, S & Blandino, G 2008, 'The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs', Cell Cycle, vol. 7, no. 21, pp. 3440-3447.
Di Agostino S, Cortese G, Monti O, Dell'Orso S, Sacchi A, Eisenstein M et al. The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs. Cell Cycle. 2008 Nov 1;7(21):3440-3447.
Di Agostino, Silvia ; Cortese, Giancarlo ; Monti, Olimpia ; Dell'Orso, Stefania ; Sacchi, Ada ; Eisenstein, Miriam ; Citro, Gennaro ; Strano, Sabrina ; Blandino, Giovanni. / The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs. In: Cell Cycle. 2008 ; Vol. 7, No. 21. pp. 3440-3447.
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