γ-Secretase Dependent Nuclear Targeting of Dystroglycan

8Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

This article is free to access.

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. 117: 2149–2157, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

Cite

CITATION STYLE

APA

Leocadio, D., Mitchell, A., & Winder, S. J. (2016). γ-Secretase Dependent Nuclear Targeting of Dystroglycan. Journal of Cellular Biochemistry, 2149–2157. https://doi.org/10.1002/jcb.25537

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free