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Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates
ER-associated degradation (ERAD) rids the early secretory pathway of misfolded or misprocessed proteins. Some members of the protein disulfide isomerase (PDI) family appear to facilitate ERAD substrate selection and retrotranslocation, but a thorough characterization of PDIs during the degradation o...
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/PMC3279382/ https://www.ncbi.nlm.nih.gov/pubmed/22190736 http://dx.doi.org/10.1091/mbc.E11-08-0704 |
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author | Grubb, Sarah Guo, Liang Fisher, Edward A. Brodsky, Jeffrey L. |
author_facet | Grubb, Sarah Guo, Liang Fisher, Edward A. Brodsky, Jeffrey L. |
author_sort | Grubb, Sarah |
collection | PubMed |
description | ER-associated degradation (ERAD) rids the early secretory pathway of misfolded or misprocessed proteins. Some members of the protein disulfide isomerase (PDI) family appear to facilitate ERAD substrate selection and retrotranslocation, but a thorough characterization of PDIs during the degradation of diverse substrates has not been undertaken, in part because there are 20 PDI family members in mammals. PDIs can also exhibit disulfide redox, isomerization, and/or chaperone activity, but which of these activities is required for the ERAD of different substrate classes is unknown. We therefore examined the fates of unique substrates in yeast, which expresses five PDIs. Through the use of a yeast expression system for apolipoprotein B (ApoB), which is disulfide rich, we discovered that Pdi1 interacts with ApoB and facilitates degradation through its chaperone activity. In contrast, Pdi1's redox activity was required for the ERAD of CPY* (a misfolded version of carboxypeptidase Y that has five disulfide bonds). The ERAD of another substrate, the alpha subunit of the epithelial sodium channel, was Pdi1 independent. Distinct effects of mammalian PDI homologues on ApoB degradation were then observed in hepatic cells. These data indicate that PDIs contribute to the ERAD of proteins through different mechanisms and that PDI diversity is critical to recognize the spectrum of potential ERAD substrates. |
format | Online Article Text |
id | pubmed-3279382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32793822012-04-30 Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates Grubb, Sarah Guo, Liang Fisher, Edward A. Brodsky, Jeffrey L. Mol Biol Cell Articles ER-associated degradation (ERAD) rids the early secretory pathway of misfolded or misprocessed proteins. Some members of the protein disulfide isomerase (PDI) family appear to facilitate ERAD substrate selection and retrotranslocation, but a thorough characterization of PDIs during the degradation of diverse substrates has not been undertaken, in part because there are 20 PDI family members in mammals. PDIs can also exhibit disulfide redox, isomerization, and/or chaperone activity, but which of these activities is required for the ERAD of different substrate classes is unknown. We therefore examined the fates of unique substrates in yeast, which expresses five PDIs. Through the use of a yeast expression system for apolipoprotein B (ApoB), which is disulfide rich, we discovered that Pdi1 interacts with ApoB and facilitates degradation through its chaperone activity. In contrast, Pdi1's redox activity was required for the ERAD of CPY* (a misfolded version of carboxypeptidase Y that has five disulfide bonds). The ERAD of another substrate, the alpha subunit of the epithelial sodium channel, was Pdi1 independent. Distinct effects of mammalian PDI homologues on ApoB degradation were then observed in hepatic cells. These data indicate that PDIs contribute to the ERAD of proteins through different mechanisms and that PDI diversity is critical to recognize the spectrum of potential ERAD substrates. The American Society for Cell Biology 2012-02-15 /pmc/articles/PMC3279382/ /pubmed/22190736 http://dx.doi.org/10.1091/mbc.E11-08-0704 Text en © 2012 Grubb 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 Grubb, Sarah Guo, Liang Fisher, Edward A. Brodsky, Jeffrey L. Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates |
title | Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates |
title_full | Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates |
title_fullStr | Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates |
title_full_unstemmed | Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates |
title_short | Protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein B and other substrates |
title_sort | protein disulfide isomerases contribute differentially to the endoplasmic reticulum–associated degradation of apolipoprotein b and other substrates |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279382/ https://www.ncbi.nlm.nih.gov/pubmed/22190736 http://dx.doi.org/10.1091/mbc.E11-08-0704 |
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