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Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation
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 c...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315801/ https://www.ncbi.nlm.nih.gov/pubmed/22298424 http://dx.doi.org/10.1091/mbc.E11-08-0722 |
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author | Izawa, Toshiaki Nagai, Hiroyuki Endo, Toshiya Nishikawa, Shuh-ichi |
author_facet | Izawa, Toshiaki Nagai, Hiroyuki Endo, Toshiya Nishikawa, Shuh-ichi |
author_sort | Izawa, Toshiaki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3315801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33158012012-06-16 Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation Izawa, Toshiaki Nagai, Hiroyuki Endo, Toshiya Nishikawa, Shuh-ichi Mol Biol Cell Articles 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. The American Society for Cell Biology 2012-04-01 /pmc/articles/PMC3315801/ /pubmed/22298424 http://dx.doi.org/10.1091/mbc.E11-08-0722 Text en © 2012 Izawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Izawa, Toshiaki Nagai, Hiroyuki Endo, Toshiya Nishikawa, Shuh-ichi Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation |
title | Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation |
title_full | Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation |
title_fullStr | Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation |
title_full_unstemmed | Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation |
title_short | Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation |
title_sort | yos9p and hrd1p mediate er retention of misfolded proteins for er-associated degradation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315801/ https://www.ncbi.nlm.nih.gov/pubmed/22298424 http://dx.doi.org/10.1091/mbc.E11-08-0722 |
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