Understanding Life and Death at CD95
CD95 (APO-1/Fas) is a member of the death receptor (DR) family, a subfamily of the TNF-R (tumor necrosis factor receptor) superfamily. Engagement of CD95 leads to the induction of the apoptotic and non-apoptotic signaling pathways. Here we addressed the question of crosstalk between CD95-induced apoptosis and NF-κB activation. Using HeLa-CD95 cells (HeLa cells stably overexpressing CD95) we have demonstrated that CD95 stimulation results in the induction of both life and death pathways. We have shown that DED proteins of the DISC, procaspase-8 and c-FLIP, regulate both pathways in a dynamic way. The data generated in this study are currently used for building a systems biology model of life/death decisions at CD95.
KeywordsCD95 Stimulation Effector Caspase Activity Total Cellular Lysate CD95 Disc Death Receptor Stimulation
We acknowledge support by the Helmholtz Alliance on Systems Biology (NW1SBCancer/UniHD) and the BMBF funded ForSys centre VIROQUANT (0313923). We also thank the Wilhelm Sander Stiftung, Helmholtz-Russia Joint Research Groups-2008-2, SFB 405 and the Tumorzentrum Heidelberg/Mannheim for supporting our work.
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