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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...

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Autores principales: Grubb, Sarah, Guo, Liang, Fisher, Edward A., Brodsky, Jeffrey L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
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.
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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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