Identification of essential sequences for cellular localization in the muscle-specific ubiquitin E3 ligase MAFbx/Atrogin 1

FEBS Lett. 2012 Feb 17;586(4):362-7. doi: 10.1016/j.febslet.2011.12.031. Epub 2012 Jan 11.


In skeletal muscle atrophy, upregulation and nuclear accumulation of the Ubiquitin E3 ligase MAFbx is essential for accelerated muscle protein loss, but the nuclear/cytoplasmic shuttling of MAFbx is undefined. Here we found that MAFbx contains two functional nuclear localization signals (NLS). Mutation or deletion of only one NLS induced cytoplasmic localization of MAFbx. We identified a non-classical NES located in the leucine charged domain (LCD) of MAFbx, which is leptomycin B insensitive. We demonstrated that mutation (L169Q) in LLXXL motif of LCD suppressed cytoplasmic retention of MAFbx. Nucleocytoplasmic shuttling of MAFbx represents a novel mechanism for targeting its substrates and its cytosolic partners in muscle atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Active Transport, Cell Nucleus / genetics
  • Active Transport, Cell Nucleus / physiology
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Conserved Sequence
  • Fatty Acids, Unsaturated / pharmacology
  • Humans
  • Mice
  • Molecular Sequence Data
  • Muscle Proteins / chemistry*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism
  • Mutagenesis, Site-Directed
  • Nuclear Localization Signals / chemistry
  • Nuclear Localization Signals / genetics
  • Nuclear Localization Signals / metabolism
  • Protein Structure, Tertiary
  • SKP Cullin F-Box Protein Ligases / chemistry*
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Sequence Deletion
  • Sequence Homology, Amino Acid


  • Fatty Acids, Unsaturated
  • Muscle Proteins
  • Nuclear Localization Signals
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • leptomycin B