Abstract
Members of the tumour necrosis factor receptor family that contain a death domain have pleiotropic activities. They induce apoptosis via interaction with intracellular FADD/MORT1 and trigger cell growth or differentiation via TRADD and TRAF molecules. The impact of FADD/MORT1-transduced signals on T lymphocyte development was investigated in transgenic mice expressing a dominant negative mutant protein, FADD-DN. Unexpectedly, FADD-DN enhanced negative selection of self-reactive thymic lymphocytes and inhibited T cell activation by increasing apoptosis. Thus signalling through FADD/MORT1 does not lead exclusively to cell death, but under certain circumstances can promote cell survival and proliferation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Apoptosis / drug effects
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Apoptosis / genetics
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Apoptosis / physiology
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Carrier Proteins / genetics*
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Carrier Proteins / pharmacology
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Carrier Proteins / physiology
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Cell Division / drug effects
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Cell Division / physiology
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Cells, Cultured
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Clone Cells / drug effects
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Clone Cells / physiology
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Fas-Associated Death Domain Protein
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Genes, Dominant / genetics
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Genes, Dominant / physiology
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Humans
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred C57BL
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Mice, Inbred MRL lpr
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Mice, Transgenic
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Mitogens / pharmacology
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Mutation / genetics
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Mutation / physiology
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Serpins / genetics
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Serpins / physiology
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Superantigens / physiology
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T-Lymphocytes / drug effects
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T-Lymphocytes / physiology*
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Thymus Gland / cytology
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Thymus Gland / drug effects
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Thymus Gland / immunology*
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Transduction, Genetic
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fas Receptor / genetics
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fas Receptor / pharmacology
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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FADD protein, human
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Fadd protein, mouse
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Fas-Associated Death Domain Protein
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Mitogens
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Serpins
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Superantigens
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fas Receptor