Targeting the ubiquitin E3 ligase MuRF1 to inhibit muscle atrophy

Cell Biochem Biophys. 2011 Jun;60(1-2):113-8. doi: 10.1007/s12013-011-9175-7.


Progressive muscle wasting, also known as myopathy or muscle atrophy is a debilitating and life-threatening disorder. Myopathy is a pathological condition of many diseases including cancer, diabetes, COPD, and AIDS and is a natural consequence of inactivity and aging (sarcopenia). Muscle atrophy occurs when there is a net loss of muscle mass resulting in a change in the balance between protein synthesis and protein degradation. The ubiquitin pathway and specific ubiquitin pathway enzymes have been directly implicated in the progression of atrophy. The ubiquitin E3 ligase Muscle-specific RING Finger E3 ligase (MuRF1) is upregulated and increases protein degradation and muscle wasting in numerous muscle atrophy models. The inhibition of MuRF1 could be a novel mechanism to prevent or reverse muscle wasting associated with various pathologies. We screened a small molecule library for inhibitors to MuRF1 activity and identified P013222, an inhibitor of MuRF1 autoubiquitylation. Further, P013222 was shown to inhibit MuRF1-dependent substrate ubiquitylation, and was active in inhibiting MuRF1 in a cellular atrophy model. Thus MuRF1 can be targeted in a specific manner and produce positive results in cellular atrophy models.

MeSH terms

  • Animals
  • Biocatalysis / drug effects
  • Blotting, Western
  • Cell Line
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Glucocorticoids / pharmacology
  • Muscle Proteins / antagonists & inhibitors*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / prevention & control*
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / drug effects
  • Myoblasts, Skeletal / metabolism
  • Myosin Heavy Chains / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Small Molecule Libraries
  • Substrate Specificity
  • Tripartite Motif Proteins
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / antagonists & inhibitors*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination / drug effects


  • Enzyme Inhibitors
  • Glucocorticoids
  • Muscle Proteins
  • Recombinant Proteins
  • Small Molecule Libraries
  • Tripartite Motif Proteins
  • Ubiquitin
  • Dexamethasone
  • TRIM63 protein, human
  • Ubiquitin-Protein Ligases
  • Myosin Heavy Chains