title: Rescue of nonsense mutations by amlexanox in human cells.
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.
authors.affiliation: Université Lille Nord de France, IFR142, Lille, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Gonzalez-Hilarion
authors.forename: Terence
authors.initials: T
authors.lastname: Beghyn
authors.forename: Jieshuang
authors.initials: J
authors.lastname: Jia
authors.forename: Nadège
authors.initials: N
authors.lastname: Debreuck
authors.forename: Gonzague
authors.initials: G
authors.lastname: Berte
authors.forename: Kamel
authors.initials: K
authors.lastname: Mamchaoui
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Dieter C
authors.initials: DC
authors.lastname: Gruenert
authors.forename: Benoit
authors.initials: B
authors.lastname: Déprez
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lejeune
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D018389:Codon, Nonsense / Q000187:drug effects* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D059365:Nonsense Mediated mRNA Decay / Q000187:drug effects* / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D018389:Codon, Nonsense; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C045742:amlexanox