Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model - PubMed (original) (raw)
. 2012 Jul 27;47(2):306-19.
doi: 10.1016/j.molcel.2012.05.006. Epub 2012 Jun 7.
Affiliations
- PMID: 22683265
- DOI: 10.1016/j.molcel.2012.05.006
Free article
Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model
Kolja Schleich et al. Mol Cell. 2012.
Free article
Abstract
The CD95 (Fas/APO-1) death-inducing signaling complex (DISC) is essential for the initiation of CD95-mediated apoptotic and nonapoptotic responses. The CD95 DISC comprises CD95, FADD, procaspase-8, procaspase-10, and c-FLIP proteins. Procaspase-8 and procaspase-10 are activated at the DISC, leading to the formation of active caspases and apoptosis initiation. In this study we analyzed the stoichiometry of the CD95 DISC. Using quantitative western blots, mass spectrometry, and mathematical modeling, we reveal that the amount of DED proteins procaspase-8/procaspase-10 and c-FLIP at the DISC exceeds that of FADD by several-fold. Furthermore, our findings imply that procaspase-8, procaspase-10, and c-FLIP could form DED chains at the DISC, enabling the formation of dimers and efficient activation of caspase-8. Taken together, our findings provide an enhanced understanding of caspase-8 activation and initiation of apoptosis at the DISC.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous