1. FADD/MORT1 and Caspase-8 Are Recruited to TRAIL Receptors 1 and 2 and Are Essential for Apoptosis Mediated by TRAIL Receptor 2
- Author
-
Peter Juo, John Blenis, Peter H. Krammer, Henning Walczak, Markus A. Weigand, Charles Rauch, Martin R. Sprick, and Eva Rieser
- Subjects
Fas-Associated Death Domain Protein ,T-Lymphocytes ,Immunology ,Apoptosis ,urologic and male genital diseases ,Caspase 8 ,Jurkat cells ,Receptors, Tumor Necrosis Factor ,Cell Line ,Jurkat Cells ,Tumor Cells, Cultured ,Humans ,Immunology and Allergy ,fas Receptor ,FADD ,Receptor ,Adaptor Proteins, Signal Transducing ,B-Lymphocytes ,biology ,Signal transducing adaptor protein ,TRADD ,Caspase 9 ,Receptors, TNF-Related Apoptosis-Inducing Ligand ,Infectious Diseases ,Caspases ,Death-inducing signaling complex ,biology.protein ,Cancer research ,biological phenomena, cell phenomena, and immunity ,Carrier Proteins ,Signal Transduction - Abstract
Apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO-2L) has been shown to exert important functions during various immunological processes. The involvement of the death adaptor proteins FADD/MORT1, TRADD, and RIP and the apoptosis-initiating caspases-8 and -10 in death signaling by the two death-inducing TRAIL receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are controversial. Analysis of the native TRAIL death-inducing signaling complex (DISC) revealed ligand-dependent recruitment of FADD/MORT1 and caspase-8. Differential precipitation of ligand-stimulated TRAIL receptors demonstrated that FADD/MORT1 and caspase-8 were recruited to TRAIL-R1 and TRAIL-R2 independently of each other. FADD/MORT1- and caspase-8-deficient Jurkat cells expressing only TRAIL-R2 were resistant to TRAIL-induced apoptosis. Thus, FADD/MORT1 and caspase-8 are essential for apoptosis induction via TRAIL-R2.
- Published
- 2000
- Full Text
- View/download PDF