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The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast
How misfolded proteins are exported from the ER to the cytosol for degradation (ER-associated Degradation, ERAD) and which proteins are participating in this process is not understood. Several studies using a single, leaky mutant indicated that Sec63p might be involved in ERAD. More recently, Sec63p...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852996/ https://www.ncbi.nlm.nih.gov/pubmed/24324744 http://dx.doi.org/10.1371/journal.pone.0082058 |
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author | Servas, Christina Römisch, Karin |
author_facet | Servas, Christina Römisch, Karin |
author_sort | Servas, Christina |
collection | PubMed |
description | How misfolded proteins are exported from the ER to the cytosol for degradation (ER-associated Degradation, ERAD) and which proteins are participating in this process is not understood. Several studies using a single, leaky mutant indicated that Sec63p might be involved in ERAD. More recently, Sec63p was also found strongly associated with proteasomes attached to the protein-conducting channel in the ER membrane which presumably form part of the export machinery. These observations prompted us to reinvestigate the role of Sec63p in ERAD by generating new mutants which were selected in a screen monitoring the intracellular accumulation of the ERAD substrate CPY*. We show that a mutation in the DnaJ-domain of Sec63p causes a defect in ERAD, whereas mutations in the Brl, acidic, and transmembrane domains only affect protein import into the ER. Unexpectedly, mutations in the acidic domain which mediates interaction of Sec63p with Sec62p also caused defects in cotranslational import. In contrast to mammalian cells where SEC63 expression levels affect steady-state levels of multi-spanning transmembrane proteins, the sec63 J-domain mutant was only defective in ERAD of soluble substrates. |
format | Online Article Text |
id | pubmed-3852996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38529962013-12-09 The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast Servas, Christina Römisch, Karin PLoS One Research Article How misfolded proteins are exported from the ER to the cytosol for degradation (ER-associated Degradation, ERAD) and which proteins are participating in this process is not understood. Several studies using a single, leaky mutant indicated that Sec63p might be involved in ERAD. More recently, Sec63p was also found strongly associated with proteasomes attached to the protein-conducting channel in the ER membrane which presumably form part of the export machinery. These observations prompted us to reinvestigate the role of Sec63p in ERAD by generating new mutants which were selected in a screen monitoring the intracellular accumulation of the ERAD substrate CPY*. We show that a mutation in the DnaJ-domain of Sec63p causes a defect in ERAD, whereas mutations in the Brl, acidic, and transmembrane domains only affect protein import into the ER. Unexpectedly, mutations in the acidic domain which mediates interaction of Sec63p with Sec62p also caused defects in cotranslational import. In contrast to mammalian cells where SEC63 expression levels affect steady-state levels of multi-spanning transmembrane proteins, the sec63 J-domain mutant was only defective in ERAD of soluble substrates. Public Library of Science 2013-12-04 /pmc/articles/PMC3852996/ /pubmed/24324744 http://dx.doi.org/10.1371/journal.pone.0082058 Text en © 2013 Servas, Römisch http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Servas, Christina Römisch, Karin The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast |
title | The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast |
title_full | The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast |
title_fullStr | The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast |
title_full_unstemmed | The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast |
title_short | The Sec63p J-Domain Is Required for ERAD of Soluble Proteins in Yeast |
title_sort | sec63p j-domain is required for erad of soluble proteins in yeast |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852996/ https://www.ncbi.nlm.nih.gov/pubmed/24324744 http://dx.doi.org/10.1371/journal.pone.0082058 |
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