The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle.

By B. A. Clarke, D. Drujan, M. Willis, Leon O. Murphy, R. A. Corpina, E. Burova, S. Rakhilin, T. Stitt, C. Patterson, E. Latres and 1 more. Cell Metabolism, 2007

700 citations recorded by the source corpus.

Skeletal muscle atrophy occurs as a side effect of treatment with synthetic glucocorticoids such as dexamethasone (DEX) and is a hallmark of cachectic syndromes associated with increased cortisol levels. The E3 ubiquitin ligase MuRF1 (muscle RING finger protein 1) is transcriptionally upregulated by DEX treatment. Differentiated myotubes treated with DEX undergo depletion of myosin heavy chain protein (MYH), which physically associates with MuRF1. This loss of MYH can be blocked by inhibition of MuRF1 expression. When wild-type and MuRF1(-/-) mice are treated with DEX, the MuRF1(-/-) animals exhibit a relative sparing of MYH. In vitro, MuRF1 is shown to function as an E3 ubiquitin ligase for MYH. These data identify the mechanism by which MYH is depleted under atrophy conditions and demonstrate that inhibition of a single E3 ligase, MuRF1, is sufficient to maintain this important sarcomeric protein.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d2923e3ccefadb0433c8b67f0f6d0a521a3c1f8f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. M. Sandri
2. D. Glass
3. A. Goldberg
4. S. Schiaffino
5. J. Zierath
6. B. Egan
7. C. Mammucari
8. Carlo Reggiani

In Molecular Biology

1. M. Sandri
2. S. Schiaffino
3. P. Bonaldo
4. C. Mammucari
5. A. Goldberg
6. J. Zierath
7. P. Delafontaine
8. Tadashi Yoshida

Citations in the corpus

• Exercise metabolism and the molecular regulation of skeletal muscle adaptation. (2013, background): “For instance, MHC degradation is regulated by MuRF1-dependent ubiquitination (Clarke et al., 2007).”
• Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models (2011, background): “MuRF1 is involved in the degradation of myosin heavy chains and other thick filament proteins, such as myosin light chains and myosin-binding protein C [ 95 ,96].”
• Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy (2020, background): “For MuRF1, myosin heavy chain (MYH) was identified as its target in Dex-induced myotube atrophy model [42].”
• Glucocorticoid-induced skeletal muscle atrophy. (2013, background): “Please cite this article in press as: Schakman O, et al. Glucocorticoidhttp://dx.doi.org/10.1016/j.biocel.2013.05.036 Abbreviations: FOXO, forkhead box O; GC, glucocorticoids; MuRF-1, muscle ING-finger protein-1; mTOR, mammalian target of rapamycin; IGF-I, Insulin-like rowth Factor-I; eIF4E, eukaryo”
• Cellular and molecular mechanisms of muscle atrophy (2013, background): “, 2004), myosin heavy chains (Clarke et al., 2007; Fielitz et al., 2007), myosin binding protein C and myosin light chain (Cohen et al.”
• During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation (2009, background): “, 2004) and myosin heavy chain (MyHC) (Clarke et al., 2007), the role of MuRF1 in degrading specific myofibrillar or soluble proteins in skeletal muscle is unknown.”
• Fiber types in mammalian skeletal muscles. (2011, background): “The halflife of MyHCs may also change due to increased protein degradation: the E3 ubiquitin ligase MuRF1 is activated in atrophying muscle and is responsible for MyHC degradation (153, 161, 218); however, there is no evidence for isoform-specific accelerated degradation of MyHC in muscles undergoin”