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γ‐Secretase Dependent Nuclear Targeting of Dystroglycan

Dystroglycan is frequently lost in adenocarcinoma. α‐dystroglycan is known to become hypoglycosylated due to transcriptional silencing of LARGE, whereas β‐dystroglycan is proteolytically cleaved and degraded. The mechanism and proteases involved in the cleavage events affecting β‐dystroglycan are po...

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Detalles Bibliográficos
Autores principales: Leocadio, Daniel, Mitchell, Andrew, Winder, Steve J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982099/
https://www.ncbi.nlm.nih.gov/pubmed/26990187
http://dx.doi.org/10.1002/jcb.25537
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author Leocadio, Daniel
Mitchell, Andrew
Winder, Steve J.
author_facet Leocadio, Daniel
Mitchell, Andrew
Winder, Steve J.
author_sort Leocadio, Daniel
collection PubMed
description Dystroglycan is frequently lost in adenocarcinoma. α‐dystroglycan is known to become hypoglycosylated due to transcriptional silencing of LARGE, whereas β‐dystroglycan is proteolytically cleaved and degraded. The mechanism and proteases involved in the cleavage events affecting β‐dystroglycan are poorly understood. Using LNCaP prostate cancer cells as a model system, we have investigated proteases and tyrosine phosphorylation affecting β‐dystroglycan proteolysis and nuclear targeting. Cell density or phorbol ester treatment increases dystroglycan proteolysis, whereas furin or γ‐secretase inhibitors decreased dystroglycan proteolysis. Using resveratrol treatment of LNCaP cells cultured at low cell density in order to up‐regulate notch and activate proteolysis, we identified significant increases in the levels of a 26 kDa β‐dystroglycan fragment. These data, therefore, support a cell density‐dependent γ‐secretase and furin mediated proteolysis of β‐dystroglycan, which could be notch stimulated, leading to nuclear targeting and subsequent degradation. 117: 2149–2157, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
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spelling pubmed-49820992016-08-26 γ‐Secretase Dependent Nuclear Targeting of Dystroglycan Leocadio, Daniel Mitchell, Andrew Winder, Steve J. J Cell Biochem Articles Dystroglycan is frequently lost in adenocarcinoma. α‐dystroglycan is known to become hypoglycosylated due to transcriptional silencing of LARGE, whereas β‐dystroglycan is proteolytically cleaved and degraded. The mechanism and proteases involved in the cleavage events affecting β‐dystroglycan are poorly understood. Using LNCaP prostate cancer cells as a model system, we have investigated proteases and tyrosine phosphorylation affecting β‐dystroglycan proteolysis and nuclear targeting. Cell density or phorbol ester treatment increases dystroglycan proteolysis, whereas furin or γ‐secretase inhibitors decreased dystroglycan proteolysis. Using resveratrol treatment of LNCaP cells cultured at low cell density in order to up‐regulate notch and activate proteolysis, we identified significant increases in the levels of a 26 kDa β‐dystroglycan fragment. These data, therefore, support a cell density‐dependent γ‐secretase and furin mediated proteolysis of β‐dystroglycan, which could be notch stimulated, leading to nuclear targeting and subsequent degradation. 117: 2149–2157, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. John Wiley and Sons Inc. 2016-03-31 2016-09 /pmc/articles/PMC4982099/ /pubmed/26990187 http://dx.doi.org/10.1002/jcb.25537 Text en © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Leocadio, Daniel
Mitchell, Andrew
Winder, Steve J.
γ‐Secretase Dependent Nuclear Targeting of Dystroglycan
title γ‐Secretase Dependent Nuclear Targeting of Dystroglycan
title_full γ‐Secretase Dependent Nuclear Targeting of Dystroglycan
title_fullStr γ‐Secretase Dependent Nuclear Targeting of Dystroglycan
title_full_unstemmed γ‐Secretase Dependent Nuclear Targeting of Dystroglycan
title_short γ‐Secretase Dependent Nuclear Targeting of Dystroglycan
title_sort γ‐secretase dependent nuclear targeting of dystroglycan
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982099/
https://www.ncbi.nlm.nih.gov/pubmed/26990187
http://dx.doi.org/10.1002/jcb.25537
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