The Role of N-Glycosylation in CD95-Induced Apoptosis
Author Information
Author(s): Shatnyeva Olga M., Kubarenko Andriy V., Weber Claudia E. M., Pappa Alexander, Schwartz-Albiez Reinhard, Weber Alexander N. R., Krammer Peter H., Lavrik Inna N.
Primary Institution: German Cancer Research Center, Heidelberg, Germany
Hypothesis
How does glycosylation of CD95 influence apoptosis initiation and procaspase-8 activation?
Conclusion
N-deglycosylation of CD95 reduces procaspase-8 activation at the DISC but does not block DISC formation.
Supporting Evidence
- N-glycosylation sites at N118 and N136 were confirmed through site-directed mutagenesis.
- In silico modeling suggested that N-glycosylation may influence the stability of the CD95 DISC complex.
- Deglycosylation of CD95 led to slower kinetics of procaspase-8 activation at the DISC.
- CD95 DISC formation was not blocked by N-deglycosylation.
- Treatment with Vibrio cholerae neuraminidase resulted in decreased amounts of active procaspase-8 at the DISC.
Takeaway
This study looks at how sugar molecules attached to a protein called CD95 affect how cells die. It finds that removing these sugars slows down the process of cell death but doesn't stop it.
Methodology
The study used in silico modeling, generation of CD95 glycosylation mutants, and biochemical analysis to assess the role of N-glycosylation in apoptosis.
Limitations
The presence of endogenous CD95 in stable cell lines complicated the analysis of the effects of deglycosylated CD95.
Digital Object Identifier (DOI)
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