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Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases.
Moresi, Viviana; Williams, Andrew H; Meadows, Eric; Flynn, Jesse M; Potthoff, Matthew J; McAnally, John; Shelton, John M; Backs, Johannes; Klein, William H; Richardson, James A; Bassel-Duby, Rhonda; Olson, Eric N.
Afiliação
  • Moresi V; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell ; 143(1): 35-45, 2010 Oct 01.
Article em En | MEDLINE | ID: mdl-20887891
Maintenance of skeletal muscle structure and function requires innervation by motor neurons, such that denervation causes muscle atrophy. We show that myogenin, an essential regulator of muscle development, controls neurogenic atrophy. Myogenin is upregulated in skeletal muscle following denervation and regulates expression of the E3 ubiquitin ligases MuRF1 and atrogin-1, which promote muscle proteolysis and atrophy. Deletion of myogenin from adult mice diminishes expression of MuRF1 and atrogin-1 in denervated muscle and confers resistance to atrophy. Mice lacking histone deacetylases (HDACs) 4 and 5 in skeletal muscle fail to upregulate myogenin and also preserve muscle mass following denervation. Conversely, forced expression of myogenin in skeletal muscle of HDAC mutant mice restores muscle atrophy following denervation. Thus, myogenin plays a dual role as both a regulator of muscle development and an inducer of neurogenic atrophy. These findings reveal a specific pathway for muscle wasting and potential therapeutic targets for this disorder.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Miogenina / Músculo Esquelético / Ubiquitina-Proteína Ligases / Proteínas Ligases SKP Culina F-Box / Histona Desacetilases / Proteínas Musculares Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Miogenina / Músculo Esquelético / Ubiquitina-Proteína Ligases / Proteínas Ligases SKP Culina F-Box / Histona Desacetilases / Proteínas Musculares Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article