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Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc
Regulatory pathways for protein glycosylation are poorly understood, but expression of branchpoint enzymes is critical. A key branchpoint enzyme is the T-synthase, which directs synthesis of the common core 1 O-glycan structure (T-antigen), the precursor structure for most mucin-type O-glycans in a...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500138/ https://www.ncbi.nlm.nih.gov/pubmed/18695044 http://dx.doi.org/10.1083/jcb.200711151 |
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author | Ju, Tongzhong Aryal, Rajindra P. Stowell, Caleb J. Cummings, Richard D. |
author_facet | Ju, Tongzhong Aryal, Rajindra P. Stowell, Caleb J. Cummings, Richard D. |
author_sort | Ju, Tongzhong |
collection | PubMed |
description | Regulatory pathways for protein glycosylation are poorly understood, but expression of branchpoint enzymes is critical. A key branchpoint enzyme is the T-synthase, which directs synthesis of the common core 1 O-glycan structure (T-antigen), the precursor structure for most mucin-type O-glycans in a wide variety of glycoproteins. Formation of active T-synthase, which resides in the Golgi apparatus, requires a unique molecular chaperone, Cosmc, encoded on Xq24. Cosmc is the only molecular chaperone known to be lost through somatic acquired mutations in cells. We show that Cosmc is an endoplasmic reticulum (ER)–localized adenosine triphosphate binding chaperone that binds directly to human T-synthase. Cosmc prevents the aggregation and ubiquitin-mediated degradation of the T-synthase. These results demonstrate that Cosmc is a molecular chaperone in the ER required for this branchpoint glycosyltransferase function and show that expression of the disease-related Tn antigen can result from deregulation or loss of Cosmc function. |
format | Text |
id | pubmed-2500138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25001382009-02-11 Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc Ju, Tongzhong Aryal, Rajindra P. Stowell, Caleb J. Cummings, Richard D. J Cell Biol Research Articles Regulatory pathways for protein glycosylation are poorly understood, but expression of branchpoint enzymes is critical. A key branchpoint enzyme is the T-synthase, which directs synthesis of the common core 1 O-glycan structure (T-antigen), the precursor structure for most mucin-type O-glycans in a wide variety of glycoproteins. Formation of active T-synthase, which resides in the Golgi apparatus, requires a unique molecular chaperone, Cosmc, encoded on Xq24. Cosmc is the only molecular chaperone known to be lost through somatic acquired mutations in cells. We show that Cosmc is an endoplasmic reticulum (ER)–localized adenosine triphosphate binding chaperone that binds directly to human T-synthase. Cosmc prevents the aggregation and ubiquitin-mediated degradation of the T-synthase. These results demonstrate that Cosmc is a molecular chaperone in the ER required for this branchpoint glycosyltransferase function and show that expression of the disease-related Tn antigen can result from deregulation or loss of Cosmc function. The Rockefeller University Press 2008-08-11 /pmc/articles/PMC2500138/ /pubmed/18695044 http://dx.doi.org/10.1083/jcb.200711151 Text en © 2008 Ju et al. 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.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Ju, Tongzhong Aryal, Rajindra P. Stowell, Caleb J. Cummings, Richard D. Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc |
title | Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc |
title_full | Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc |
title_fullStr | Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc |
title_full_unstemmed | Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc |
title_short | Regulation of protein O-glycosylation by the endoplasmic reticulum–localized molecular chaperone Cosmc |
title_sort | regulation of protein o-glycosylation by the endoplasmic reticulum–localized molecular chaperone cosmc |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500138/ https://www.ncbi.nlm.nih.gov/pubmed/18695044 http://dx.doi.org/10.1083/jcb.200711151 |
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