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  • Original Article
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Modulation of Nr-13 antideath activity by peptide aptamers

Abstract

Tumor cells are characterized by deregulated proliferation and resistance to proapoptotic stimuli. The Bcl-2 family of antiapoptotic proteins is overexpressed in a large number of chemoresistant tumors. Downregulation or inhibition of antiapoptotic proteins might result in the sensitization of cancer cells to chemotherapeutic agents. In the present study, we took advantage of the peptide aptamer strategy to target Nr-13, a Bcl-2 antiapoptotic protein involved in neoplastic transformation by the Rous sarcoma virus. We isolated peptide aptamers that behave as Nr-13 regulators, in vitro and in mammalian cells in culture. Some of these aptamers have potential proapoptotic activities. These data suggest that peptide aptamers targeting the Bcl-2 family of apoptosis inhibitors may be useful for the development of anticancer molecules.

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Acknowledgements

We thank BB Rudkin for his initial support, N Bonnefoy-Bérard for providing the bfl-1 cDNA and D Ficheux for peptide synthesis. We also thank A Cornut for her skillful assistance in protein purification. We are grateful to M Moradi-Améli for her help and advice, and T Lorca for Xenopus extracts. This work was supported by the Association pour la Recherche sur le Cancer (ARC), the Ligue Nationale Contre le Cancer and the Région Rhône-Alpes. ALN was supported by the Fondation Mérieux and the ARC. ODL was supported by Retina France, and SV was supported by the ARC.

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Correspondence to G Gillet.

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Nouvion, AL., Thibaut, J., Lohez, O. et al. Modulation of Nr-13 antideath activity by peptide aptamers. Oncogene 26, 701–710 (2007). https://doi.org/10.1038/sj.onc.1209832

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