Derlin-1 promotes ubiquitination and degradation of epithelial sodium channel (ENaC)
| Autor: | Jian Zhang, Dongming Su, Min Li, Yamei Ge, Fei Sun, Jing Xing, Xiubin Liang, Yizhi Cao, Yujie Huang, Shen Qu, Hui You |
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| Rok vydání: | 2017 |
| Předmět: |
inorganic chemicals
0301 basic medicine Epithelial sodium channel biology urogenital system Protein subunit Endoplasmic reticulum Cell Biology Plasma protein binding respiratory system Membrane transport Endoplasmic-reticulum-associated protein degradation Cell biology Ubiquitin ligase 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Biochemistry Ubiquitin biology.protein hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.198242 |
| Popis: | Ubiquitylation of the epithelial Na+ channel (ENaC) plays a critical role in cellular functions, including transmembrane transport of Na+, Na+ and water balance, and blood pressure stabilization. Published studies have suggested that ENaC subunits are targets of ER-related degradation (ERAD) in yeast systems. However, the molecular mechanism underlying proteasome-mediated degradation of ENaC subunits remains to be established. Derlin-1, an E3 ligase mediator, links recognized target proteins to ubiquitin-mediated proteasomal degradation in the cytosol. In the present study, we found that derlin-1 suppressed the expression of ENaC at the protein level and that the subunit α-ENaC (also known as SCNN1A) physically interacted with derlin-1 at the membrane-anchored domains or the loop regions, and that derlin-1 initiated α-ENaC retrotranslocation. In addition, HUWE1, an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase, was recruited and promoted K11-linked polyubiquitylation of α-ENaC and, hence, formation of an α-ENaC ubiquitin-mediated degradation complex. These findings suggest that derlin-1 promotes ENaC ubiquitylation and enhances ENaC ubiquitin- mediated proteasome degradation. The derlin-1 pathway therefore may represent a significant early checkpoint in the recognition and degradation of ENaC in mammalian cells. |
| Databáze: | OpenAIRE |
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