Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63
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 deno...
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eLife Sciences Publications Ltd
2016-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/10528 |
| _version_ | 1828375332862820352 |
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| author | Yannick von Grabowiecki Paula Abreu Orphee Blanchard Lavinia Palamiuc Samir Benosman Sophie Mériaux Véronique Devignot Isabelle Gross Georg Mellitzer José L Gonzalez de Aguilar Christian Gaiddon |
| author_facet | Yannick von Grabowiecki Paula Abreu Orphee Blanchard Lavinia Palamiuc Samir Benosman Sophie Mériaux Véronique Devignot Isabelle Gross Georg Mellitzer José L Gonzalez de Aguilar Christian Gaiddon |
| author_sort | Yannick von Grabowiecki |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:45:09Z |
| format | Article |
| id | doaj.art-4b0325c5e8ea4d2baa0a5ac56259d422 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:45:09Z |
| publishDate | 2016-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4b0325c5e8ea4d2baa0a5ac56259d4222022-12-22T02:05:21ZengeLife Sciences Publications LtdeLife2050-084X2016-02-01510.7554/eLife.10528Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63Yannick von Grabowiecki0https://orcid.org/0000-0003-2189-6953Paula Abreu1Orphee Blanchard2Lavinia Palamiuc3Samir Benosman4Sophie Mériaux5Véronique Devignot6Isabelle Gross7Georg Mellitzer8José L Gonzalez de Aguilar9Christian Gaiddon10https://orcid.org/0000-0003-4315-3851UMR_S 1113, Molecular mechanisms of stress response and pathologies, Institut national de la santé et de la recherche médicale, Strasbourg, France; Fédération de Recherche Translationnelle, Strasbourg University, Strasbourg, FranceUMR_S 1113, Molecular mechanisms of stress response and pathologies, Institut national de la santé et de la recherche médicale, Strasbourg, France; Fédération de Recherche Translationnelle, Strasbourg University, Strasbourg, FranceUMR_S 1113, Molecular mechanisms of stress response and pathologies, Institut national de la santé et de la recherche médicale, Strasbourg, France; Fédération de Recherche Translationnelle, Strasbourg University, Strasbourg, FranceFédération de Recherche Translationnelle, Strasbourg University, Strasbourg, France; Sanford Burnham Medical Research Institute, San Diego, United StatesSanford Burnham Medical Research Institute, San Diego, United StatesFédération de Recherche Translationnelle, Strasbourg University, Strasbourg, France; Sanford Burnham Medical Research Institute, San Diego, United StatesUMR_S 1113, Molecular mechanisms of stress response and pathologies, Institut national de la santé et de la recherche médicale, Strasbourg, France; Fédération de Recherche Translationnelle, Strasbourg University, Strasbourg, FranceUMR_S 1113, Molecular mechanisms of stress response and pathologies, Institut national de la santé et de la recherche médicale, Strasbourg, France; Fédération de Recherche Translationnelle, Strasbourg University, Strasbourg, FranceUMR_S 1113, Molecular mechanisms of stress response and pathologies, Institut national de la santé et de la recherche médicale, Strasbourg, France; Fédération de Recherche Translationnelle, Strasbourg University, Strasbourg, FranceFédération de Recherche Translationnelle, Strasbourg University, Strasbourg, France; Institut national de la santé et de la recherche médicale, Laboratoire SMN, Strasbourg, FranceUMR_S 1113, Molecular mechanisms of stress response and pathologies, Institut national de la santé et de la recherche médicale, Strasbourg, France; Fédération de Recherche Translationnelle, Strasbourg University, Strasbourg, FranceMechanisms 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.https://elifesciences.org/articles/10528p53p63murf-1muscle atrophyALStrim63 |
| spellingShingle | Yannick von Grabowiecki Paula Abreu Orphee Blanchard Lavinia Palamiuc Samir Benosman Sophie Mériaux Véronique Devignot Isabelle Gross Georg Mellitzer José L Gonzalez de Aguilar Christian Gaiddon Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63 eLife p53 p63 murf-1 muscle atrophy ALS trim63 |
| title | Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63 |
| title_full | Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63 |
| title_fullStr | Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63 |
| title_full_unstemmed | Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63 |
| title_short | Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63 |
| title_sort | transcriptional activator tap63 is upregulated in muscular atrophy during als and induces the pro atrophic ubiquitin ligase trim63 |
| topic | p53 p63 murf-1 muscle atrophy ALS trim63 |
| url | https://elifesciences.org/articles/10528 |
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