A novel ubiquitin-binding protein ZNF216 functioning in muscle atrophy

EMBO J. 2006 Feb 8;25(3):554-64. doi: 10.1038/sj.emboj.7600945. Epub 2006 Jan 19.


The ubiquitin-proteasome system (UPS) is critical for specific degradation of cellular proteins and plays a pivotal role on protein breakdown in muscle atrophy. Here, we show that ZNF216 directly binds polyubiquitin chains through its N-terminal A20-type zinc-finger domain and associates with the 26S proteasome. ZNF216 was colocalized with the aggresome, which contains ubiquitinylated proteins and other UPS components. Expression of Znf216 was increased in both denervation- and fasting-induced muscle atrophy and upregulated by expression of constitutively active FOXO, a master regulator of muscle atrophy. Mice deficient in Znf216 exhibited resistance to denervation-induced atrophy, and ubiquitinylated proteins markedly accumulated in neurectomized muscle compared to wild-type mice. These data suggest that ZNF216 functions in protein degradation via the UPS and plays a crucial role in muscle atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins
  • Mice
  • Mice, Knockout
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Polyubiquitin / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Up-Regulation
  • Zinc Fingers*


  • DNA-Binding Proteins
  • Muscle Proteins
  • Proteins
  • Zfp216 protein, mouse
  • Polyubiquitin
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease