Leocadio, D., Mitchell, A. and Winder, S.J. (2016) γ-Secretase Dependent Nuclear Targeting of Dystroglycan. Journal of Cellular Biochemistry, 117 (9). pp. 2149-2157. ISSN 0730-2312
Abstract
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
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 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 License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Feb 2017 15:00 |
Last Modified: | 16 Feb 2017 15:17 |
Published Version: | https://doi.org/10.1002/jcb.25537 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jcb.25537 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108330 |
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