Modulation of the CD95-induced Apoptosis: the Role of CD95 N-glycosylation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Jun 1

PMID 21625644

Citations 33

Authors

Olga M Shatnyeva

Andriy V Kubarenko

Claudia E M Weber

Alexander Pappa

Reinhard Schwartz-Albiez

Alexander N R Weber

Peter H Krammer

Inna N Lavrik

Affiliations

Soon will be listed here.

Abstract

Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems.

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