A novel ubiquitin-binding protein ZNF216 functioning in muscle atrophy.
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.
Hishiya
Akinori
A
Department of Bone & Joint Disease, National Center for Geriatrics & Gerontology, Obu, Aichi, Japan.
Iemura
Shun-ichiro
S
Natsume
Tohru
T
Takayama
Shinichi
S
Ikeda
Kyoji
K
Watanabe
Ken
K
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D011506:Proteins; C485423:Zfand5 protein, mouse; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease