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SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER

Protein quality control in the endoplasmic reticulum (ER) involves recognition of misfolded proteins and dislocation from the ER lumen into the cytosol, followed by proteasomal degradation. Viruses have co-opted this pathway to destroy proteins that are crucial for host defense. Examination of dislo...

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Detalles Bibliográficos
Autores principales: Mueller, Britta, Lilley, Brendan N., Ploegh, Hidde L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064567/
https://www.ncbi.nlm.nih.gov/pubmed/17043138
http://dx.doi.org/10.1083/jcb.200605196
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author Mueller, Britta
Lilley, Brendan N.
Ploegh, Hidde L.
author_facet Mueller, Britta
Lilley, Brendan N.
Ploegh, Hidde L.
author_sort Mueller, Britta
collection PubMed
description Protein quality control in the endoplasmic reticulum (ER) involves recognition of misfolded proteins and dislocation from the ER lumen into the cytosol, followed by proteasomal degradation. Viruses have co-opted this pathway to destroy proteins that are crucial for host defense. Examination of dislocation of class I major histocompatibility complex (MHC) heavy chains (HCs) catalyzed by the human cytomegalovirus (HCMV) immunoevasin US11 uncovered a conserved complex of the mammalian dislocation machinery. We analyze the contributions of a novel complex member, SEL1L, mammalian homologue of yHrd3p, to the dislocation process. Perturbation of SEL1L function discriminates between the dislocation pathways used by US11 and US2, which is a second HCMV protein that catalyzes dislocation of class I MHC HCs. Furthermore, reduction of the level of SEL1L by small hairpin RNA (shRNA) inhibits the degradation of a misfolded ribophorin fragment (RI(332)) independently of the presence of viral accessories. These results allow us to place SEL1L in the broader context of glycoprotein degradation, and imply the existence of multiple independent modes of extraction of misfolded substrates from the mammalian ER.
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spelling pubmed-20645672007-11-29 SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER Mueller, Britta Lilley, Brendan N. Ploegh, Hidde L. J Cell Biol Research Articles Protein quality control in the endoplasmic reticulum (ER) involves recognition of misfolded proteins and dislocation from the ER lumen into the cytosol, followed by proteasomal degradation. Viruses have co-opted this pathway to destroy proteins that are crucial for host defense. Examination of dislocation of class I major histocompatibility complex (MHC) heavy chains (HCs) catalyzed by the human cytomegalovirus (HCMV) immunoevasin US11 uncovered a conserved complex of the mammalian dislocation machinery. We analyze the contributions of a novel complex member, SEL1L, mammalian homologue of yHrd3p, to the dislocation process. Perturbation of SEL1L function discriminates between the dislocation pathways used by US11 and US2, which is a second HCMV protein that catalyzes dislocation of class I MHC HCs. Furthermore, reduction of the level of SEL1L by small hairpin RNA (shRNA) inhibits the degradation of a misfolded ribophorin fragment (RI(332)) independently of the presence of viral accessories. These results allow us to place SEL1L in the broader context of glycoprotein degradation, and imply the existence of multiple independent modes of extraction of misfolded substrates from the mammalian ER. The Rockefeller University Press 2006-10-23 /pmc/articles/PMC2064567/ /pubmed/17043138 http://dx.doi.org/10.1083/jcb.200605196 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Mueller, Britta
Lilley, Brendan N.
Ploegh, Hidde L.
SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER
title SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER
title_full SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER
title_fullStr SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER
title_full_unstemmed SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER
title_short SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER
title_sort sel1l, the homologue of yeast hrd3p, is involved in protein dislocation from the mammalian er
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064567/
https://www.ncbi.nlm.nih.gov/pubmed/17043138
http://dx.doi.org/10.1083/jcb.200605196
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