Journal article
Myogenin and Class II HDACs Control Neurogenic Muscle Atrophy by Inducing E3 Ubiquitin Ligases
Cell (Cambridge), Vol.143(1), pp.35-45
10/01/2010
DOI: 10.1016/j.cell.2010.09.004
PMCID: PMC2982779
PMID: 20887891
Abstract
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.
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► Myogenin, a key regulator of myogenesis, controls muscle atrophy upon denervation ► Adult mice lacking myogenin are resistant to muscle atrophy upon denervation ► Myogenin transcriptionally activates E3 ubiquitin ligases, which promote atrophy ► Mice lacking histone deacetylases 4 and 5 mimic mice lacking myogenin
Details
- Title: Subtitle
- Myogenin and Class II HDACs Control Neurogenic Muscle Atrophy by Inducing E3 Ubiquitin Ligases
- Creators
- Viviana Moresi - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAAndrew H Williams - The University of Texas Southwestern Medical CenterEric Meadows - Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAJesse M Flynn - Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAMatthew J Potthoff - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAJohn McAnally - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAJohn M Shelton - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAJohannes Backs - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAWilliam H Klein - Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAJames A Richardson - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USARhonda Bassel-Duby - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAEric N Olson - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.143(1), pp.35-45
- DOI
- 10.1016/j.cell.2010.09.004
- PMID
- 20887891
- PMCID
- PMC2982779
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 10/01/2010
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040544202771
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