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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...

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Detalles Bibliográficos
Autores principales: Ju, Tongzhong, Aryal, Rajindra P., Stowell, Caleb J., Cummings, Richard D.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
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.
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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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