Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1

Am J Physiol Endocrinol Metab. 2014 Sep 15;307(6):E469-84. doi: 10.1152/ajpendo.00204.2014. Epub 2014 Aug 5.

Abstract

Muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1 were identified more than 10 years ago as two muscle-specific E3 ubiquitin ligases that are increased transcriptionally in skeletal muscle under atrophy-inducing conditions, making them excellent markers of muscle atrophy. In the past 10 years much has been published about MuRF1 and MAFbx with respect to their mRNA expression patterns under atrophy-inducing conditions, their transcriptional regulation, and their putative substrates. However, much remains to be learned about the physiological role of both genes in the regulation of mass and other cellular functions in striated muscle. Although both MuRF1 and MAFbx are enriched in skeletal, cardiac, and smooth muscle, this review will focus on the current understanding of MuRF1 and MAFbx in skeletal muscle, highlighting the critical questions that remain to be answered.

Keywords: atrogenes; muscle RING finger 1; muscle atrophy F-box; muscle sparing; protein quality control; ubiquitin proteasome system.

Publication types

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

MeSH terms

  • Animals
  • Gene Expression Regulation / physiology
  • Humans
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / physiology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / enzymology*
  • Muscular Atrophy / genetics
  • Muscular Atrophy / pathology
  • Organ Size / physiology
  • Proteasome Endopeptidase Complex / metabolism
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / physiology*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology*

Substances

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