Abstract
A role for caspase-10, previously implicated in the autoimmune lymphoproliferative syndrome, in death receptor signaling has not been directly shown. Here we show that caspase-10 can function independently of caspase-8 in initiating Fas- and tumor necrosis factor-related apoptosis-inducing ligand-receptor-mediated apoptosis. Moreover, Fas crosslinking in primary human T cells leads to the recruitment and activation of caspase-10. Fluorescent resonance energy transfer analysis indicates that the death-effector domains of caspase-8 and -10 both interact with the death-effector domain of FADD. Nonetheless, we find that caspase-8 and -10 may have different apoptosis substrates and therefore potentially distinct roles in death receptor signaling or other cellular processes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Apoptosis Regulatory Proteins
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Apoptosis*
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B-Lymphocytes / cytology
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Carrier Proteins / metabolism*
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Caspase 10
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Caspase 8
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Caspase 9
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Caspases / genetics
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Caspases / metabolism*
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Cells, Cultured
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Dendritic Cells / cytology
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Dimerization
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Enzyme Activation
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Fas-Associated Death Domain Protein
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Gene Expression Profiling
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Humans
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Jurkat Cells
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Membrane Glycoproteins / metabolism
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Signal Transduction*
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T-Lymphocytes / cytology
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor-alpha / metabolism
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fas Receptor / metabolism*
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fas Receptor / pharmacology
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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Membrane Glycoproteins
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TNF-Related Apoptosis-Inducing Ligand
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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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CASP8 protein, human
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CASP9 protein, human
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Caspase 10
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Caspase 8
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Caspase 9
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Caspases
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CASP10 protein, human