NF-kappa B-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue FASEB Journal Année : 2008

NF-kappa B-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A

Beatrice Benayoun
  • Fonction : Auteur
Marc Bartoli
Nathalie Danièle
  • Fonction : Auteur
  • PersonId : 938603
Evelyne Gicquel
Nathalie Bourg
Laurence Suel
Hanns Lochmüller
Isabelle Richard

Résumé

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in the cysteine protease calpain 3 (CAPN3) that leads to selective muscle wasting. We previously showed that CAPN3 deficiency is associated with a profound perturbation of the NF-kappa B/I kappa B alpha survival pathway. In this study, the consequences of altered NF-kappa B/I kappa B alpha pathway were investigated using biological materials from LGMD2A patients. We first show that die antiapoptotic factor cellular-FUCE inhibitory protein (c-FLIP), which is dependent on the NF-kappa B pathway in normal muscle cells, is down-regulated in LGMD2A biopsies. In muscle cells isolated from LGMD2A patients, NF-kappa B is readily activated on cytokine induction as shown by an increase in its DNA binding activity. However, we observed discrepant transcriptional responses depending on the NF-kappa B target genes. I kappa B alpha is expressed following NF-kappa B activation independent of the CAPN3 status, whereas expression of c-FLIP is obtained only when CAPN3 is present. These data lead us to postulate that CAPN3 intervenes in the regulation of the expression of NF-kappa B-dependent survival genes to prevent apoptosis in skeletal muscle. Deregulations in the NF-kappa B pathway could be part of the mechanism responsible for the muscle wasting resulting from CAPN3 deficiency.
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Dates et versions

hal-01610041 , version 1 (04-10-2017)

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Beatrice Benayoun, Stephen Baghdiguian, Alicia Lajmanovich, Marc Bartoli, Nathalie Danièle, et al.. NF-kappa B-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A. FASEB Journal, 2008, 22 (5), pp.1521-1529. ⟨10.1096/fj.07-8701com⟩. ⟨hal-01610041⟩
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