Myosin accumulation and striated muscle myopathy result from the loss of muscle RING finger 1 and 3
| Autor: | Jens Fielitz, John M. Shelton, Jeffrey A. Spencer, Eric N. Olson, James A. Richardson, Rhonda S Bassel-Duby, Shuaib Latif, David J. Glass, Mi Sung Kim |
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| Přispěvatelé: | MDC Library |
| Rok vydání: | 2007 |
| Předmět: |
Male
Heart Diseases Chromosomal Proteins Non-Histone 570 Life Sciences Myosins Protein Serine-Threonine Kinases Sarcomere 610 Medical Sciences Medicine Mice Muscular Diseases Ubiquitin Myosin medicine Animals Myocyte Electron Microscopy Myopathy Mice Knockout Polycomb Repressive Complex 1 biology Cardiac muscle Skeletal muscle General Medicine Protein-Serine-Threonine Kinases Cell biology DNA-Binding Proteins Microscopy Electron medicine.anatomical_structure Proteasome Biochemistry Cardiovascular and Metabolic Diseases biology.protein medicine.symptom Protein Binding Transcription Factors Research Article |
| Zdroj: | Journal of Clinical Investigation 117 (9): 2486-2495. |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci32827 |
| Popis: | Maintenance of skeletal and cardiac muscle structure and function requires precise control of the synthesis, assembly, and turnover of contractile proteins of the sarcomere. Abnormalities in accumulation of sarcomere proteins are responsible for a variety of myopathies. However, the mechanisms that mediate turnover of these long-lived proteins remain poorly defined. We show that muscle RING finger 1 (MuRF1) and MuRF3 act as E3 ubiquitin ligases that cooperate with the E2 ubiquitin-conjugating enzymes UbcH5a, -b, and -c to mediate the degradation of beta/slow myosin heavy chain (beta/slow MHC) and MHCIIa via the ubiquitin proteasome system (UPS) in vivo and in vitro. Accordingly, mice deficient for MuRF1 and MuRF3 develop a skeletal muscle myopathy and hypertrophic cardiomyopathy characterized by subsarcolemmal MHC accumulation, myofiber fragmentation, and diminished muscle performance. These findings identify MuRF1 and MuRF3 as key E3 ubiquitin ligases for the UPS-dependent turnover of sarcomeric proteins and reveal a potential basis for myosin storage myopathies. |
| Databáze: | OpenAIRE |
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