Rescue of nonsense mutations by amlexanox in human cells.

Abstract : ABSTRACT: BACKGROUND: Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence of nonsense mutations is often the absence of mutant gene expression due to the activation of an mRNA surveillance mechanism called nonsense-mediated mRNA decay (NMD). Strategies to rescue the expression of nonsense-containing mRNAs have been developed such as NMD inhibition or nonsense mutation readthrough. METHODS: Using a dedicated screening system, we sought molecules capable to block NMD. Additionally, 3 cell lines derived from patient cells and harboring a nonsense mutation were used to study the effect of the selected molecule on the level of nonsense-containing mRNAs and the synthesis of proteins from these mutant mRNAs. RESULTS: We demonstrate here that amlexanox, a drug used for decades, not only induces an increase in nonsense-containing mRNAs amount in treated cells, but also leads to the synthesis of the full-length protein in an efficient manner. We also demonstrated that these full length proteins are functional. CONCLUSIONS: As a result of this dual activity, amlexanox may be useful as a therapeutic approach for diseases caused by nonsense mutations.
Type de document :
Article dans une revue
Orphanet Journal of Rare Diseases, BioMed Central, 2012, 7 (1), pp.58. 〈10.1186/1750-1172-7-58〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00783891
Contributeur : Ed. Bmc <>
Soumis le : vendredi 1 février 2013 - 21:16:53
Dernière modification le : mercredi 17 octobre 2018 - 19:50:49
Document(s) archivé(s) le : lundi 17 juin 2013 - 18:22:31

Identifiants

Collections

Citation

Sara Gonzalez-Hilarion, Terence Beghyn, Jieshuang Jia, Nadège Debreuck, Gonzague Berte, et al.. Rescue of nonsense mutations by amlexanox in human cells.. Orphanet Journal of Rare Diseases, BioMed Central, 2012, 7 (1), pp.58. 〈10.1186/1750-1172-7-58〉. 〈inserm-00783891〉

Partager

Métriques

Consultations de la notice

241

Téléchargements de fichiers

358