We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A novel ubiquitin-binding protein ZNF216 functioning in muscle atrophy.
- Authors
Hishiya, Akinori; Iemura, Shun-ichiro; Natsume, Tohru; Takayama, Shinichi; Ikeda, Kyoji; Watanabe, Ken
- Abstract
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.
- Subjects
CARRIER proteins; UBIQUITIN; LABORATORY mice; PROTEASE inhibitors; MUSCULAR atrophy; DENERVATION
- Publication
EMBO Journal, 2006, Vol 25, Issue 3, p554
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7600945