The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass

Free Radic Biol Med. 2016 Sep;98:218-230. doi: 10.1016/j.freeradbiomed.2015.12.031. Epub 2015 Dec 29.


The ubiquitin-proteasome system (UPS) is the main regulatory mechanism of protein degradation in skeletal muscle. The ubiquitin-ligase enzymes (E3s) have a central role in determining the selectivity and specificity of the UPS. Since their identification in 2001, the muscle specific E3s, muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx), have been shown to be implicated in the regulation of skeletal muscle atrophy in various pathological and physiological conditions. This review aims to explore the involvement of MuRF-1 and MAFbx in catabolism of skeletal muscle during various pathologies, such as cancer cachexia, sarcopenia of aging, chronic kidney disease (CKD), diabetes, and chronic obstructive pulmonary disease (COPD). In addition, the effects of various lifestyle and modifiable factors (e.g. nutrition, exercise, cigarette smoking, and alcohol) on MuRF-1 and MAFbx regulation will be discussed. Finally, evidence of potential strategies to protect against skeletal muscle wasting through inhibition of MuRF-1 and MAFbx expression will be explored.

Keywords: MAFbx; MuRF-1; Skeletal muscle loss; Ubiquitin–proteasome system.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy
  • Disease
  • Exercise
  • Humans
  • Life Style
  • Mice
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Proteasome Endopeptidase Complex / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Tripartite Motif Proteins / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitins / metabolism


  • Muscle Proteins
  • Tripartite Motif Proteins
  • Ubiquitins
  • FBXO32 protein, human
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • TRIM63 protein, human
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex