Fiche publication
Date publication
février 2016
Journal
eLife
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GAIDDON Christian
,
Dr GROSS Isabelle
,
Dr MELLITZER Georg
Tous les auteurs :
von Grabowiecki Y, Abreu P, Blanchard O, Palamiuc L, Benosman S, Mériaux S, Devignot V, Gross I, Mellitzer G, Gonzalez de Aguilar JL, Gaiddon C
Lien Pubmed
Résumé
Mechanisms of muscle atrophy are complex and their understanding might help finding therapeutic solutions for pathologies such as amyotrophic lateral sclerosis (ALS). We meta-analyzed transcriptomic experiments of muscles of ALS patients and mouse models, uncovering a p53 deregulation as common denominator. We then characterized the induction of several p53 family members (p53, p63, p73) and a correlation between the levels of p53 family target genes and the severity of muscle atrophy in ALS patients and mice. In particular, we observed increased p63 protein levels in the fibers of atrophic muscles via denervation-dependent and -independent mechanisms. At a functional level, we demonstrated that TAp63 and p53 transactivate the promoter and increased the expression of Trim63 (MuRF1), an effector of muscle atrophy. Altogether, these results suggest a novel function for p63 as a contributor to muscular atrophic processes via the regulation of multiple genes, including the muscle atrophy gene Trim63.
Mots clés
Amyotrophic Lateral Sclerosis, physiopathology, Animals, Disease Models, Animal, Gene Expression Profiling, Humans, Mice, Muscle Proteins, biosynthesis, Muscles, pathology, Transcription Factors, biosynthesis, Tripartite Motif Proteins, Tumor Suppressor Protein p53, biosynthesis, Tumor Suppressor Proteins, biosynthesis, Ubiquitin-Protein Ligases, biosynthesis, Up-Regulation
Référence
Elife. 2016 Feb;5:
