Document Detail


Modulation of the CD95-Induced Apoptosis: The Role of CD95 N-Glycosylation.
MedLine Citation:
PMID:  21625644     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
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
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Publication Detail:
Type:  Journal Article     Date:  2011-05-18
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-05-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e19927     Citation Subset:  IM    
Affiliation:
Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany.
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