|
エンドウ トシヤ
ENDO TOSHIYA
遠藤 斗志也 所属 京都産業大学 生命科学部 先端生命科学科 職種 客員教授 |
|
| 言語種別 | 英語 |
| 発行・発表の年月 | 2012/04 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation |
| 執筆形態 | その他 |
| 掲載誌名 | MOLECULAR BIOLOGY OF THE CELL |
| 出版社・発行元 | AMER SOC CELL BIOLOGY |
| 巻・号・頁 | 23(7),pp.1283-1293 |
| 著者・共著者 | Toshiaki Izawa,Hiroyuki Nagai,Toshiya Endo,Shuh-ichi Nishikawa |
| 概要 | The endoplasmic reticulum (ER) has an elaborate quality control system, which retains misfolded proteins and targets them to ER-associated protein degradation (ERAD). To analyze sorting between ER retention and ER exit to the secretory pathway, we constructed fusion proteins containing both folded carboxypeptidase Y (CPY) and misfolded mutant CPY (CPY*) units. Although the luminal Hsp70 chaperone BiP interacts with the fusion proteins containing CPY* with similar efficiency, a lectin-like ERAD factor Yos9p binds to them with different efficiency. Correlation between efficiency of Yos9p interactions and ERAD of these fusion proteins indicates that Yos9p but not BiP functions in the retention of misfolded proteins for ERAD. Yos9p targets a CPY*-containing ERAD substrate to Hrd1p E3 ligase, thereby causing ER retention of the misfolded protein. This ER retention is independent of the glycan degradation signal on the misfolded protein and operates even when proteasomal degradation is inhibited. These results collectively indicate that Yos9p and Hrd1p mediate ER retention of misfolded proteins in the early stage of ERAD, which constitutes a process separable from the later degradation step. |
| DOI | 10.1091/mbc.E11-08-0722 |
| ISSN | 1059-1524 |