Abstract
Fas (APO-1/CD95) and tumor necrosis factor receptor 1 (TNFR1) trigger apoptosis by recruiting the apoptosis initiator caspase-8 through the adaptor FADD. Fas binds FADD directly, whereas TNFR1 binds FADD indirectly, through TRADD. TRADD alternatively recruits the NF-kappaB-inducing adaptor RIP. The TNF homolog Apo2L/TRAIL triggers apoptosis through two distinct death receptors, DR4 and DR5; however, receptor over-expression studies have yielded conflicting results on the ligand's signaling mechanism. Apo2L/TRAIL induced homomeric and heteromeric complexes of DR4 and DR5 and stimulated recruitment of FADD and caspase-8 and caspase-8 activation in nontransfected cells. TRADD and RIP, which bound TNFR1, did not bind DR4 and DR5. Thus, Apo2L/TRAIL and FasL initiate apoptosis through similar mechanisms, and FADD may be a universal adaptor for death receptors.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Apoptosis / immunology*
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Apoptosis Regulatory Proteins
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Carrier Proteins / metabolism*
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Caspase 8
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Caspase 9
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Caspases / metabolism*
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Extracellular Space / metabolism
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Fas-Associated Death Domain Protein
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Humans
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Ligands
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Lymphoma, B-Cell / enzymology
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Lymphoma, B-Cell / immunology
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Lymphoma, B-Cell / metabolism
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Lymphoma, B-Cell / pathology
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Macromolecular Substances
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology*
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Models, Immunological
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Proteins / metabolism
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Receptor-Interacting Protein Serine-Threonine Kinases
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor / physiology*
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Signal Transduction / immunology
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TNF Receptor-Associated Factor 1
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / physiology*
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fas Receptor / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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Carrier Proteins
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FADD protein, human
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Fas-Associated Death Domain Protein
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Ligands
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Macromolecular Substances
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Membrane Glycoproteins
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Proteins
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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TNF Receptor-Associated Factor 1
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TNF-Related Apoptosis-Inducing Ligand
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TNFRSF10A protein, human
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TNFRSF10B protein, human
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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fas Receptor
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RIPK1 protein, human
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Receptor-Interacting Protein Serine-Threonine Kinases
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CASP8 protein, human
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CASP9 protein, human
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Caspase 8
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Caspase 9
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Caspases