Derlin-1 promotes ubiquitylation and degradation of the epithelial Na+ channel, ENaC

• DOI: 10.1242/jcs.198242
• Publication Date: 2017-01-31T01:40:33Z
• Authors: Hui You; Yamei Ge; Jian Zhang; Yizhi Cao; Jing Xing; Dongming Su; Yujie Huang; Min Li; Shen Qu; Fei Sun; Xiubin Liang
• Keywords: Epithelial sodium channel; Endoplasmic-reticulum-associated protein degradation; Deubiquitinating enzyme; Protein Degradation

Ubiquitylation of the epithelial Na+ channel (ENaC) plays a critical role in cellular functions, including transmembrane transport Na+, and water balance, blood pressure stabilization. Published studies have suggested that ENaC subunits are targets ER-related degradation (ERAD) yeast systems. However, molecular mechanism underlying proteasome-mediated remains to be established. Derlin-1, an E3 ligase mediator, links recognized target proteins ubiquitin-mediated proteasomal cytosol. In present study, we found derlin-1 suppressed expression at protein level subunit α-ENaC (also known as SCNN1A) physically interacted with membrane-anchored domains or loop regions, initiated retrotranslocation. addition, HUWE1, endoplasmic reticulum (ER)-resident ubiquitin ligase, was recruited promoted K11-linked polyubiquitylation and, hence, formation complex. These findings suggest promotes ubiquitylation enhances ubiquitin- mediated proteasome degradation. The pathway therefore may represent significant early checkpoint recognition mammalian cells.