Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1782447712950550528 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4982099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT leocadiodaniel gsecretasedependentnucleartargetingofdystroglycan AT mitchellandrew gsecretasedependentnucleartargetingofdystroglycan AT winderstevej gsecretasedependentnucleartargetingofdystroglycan |