Abstract
FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.
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*
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Transformation, Neoplastic
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Cells, Cultured
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Doxorubicin / pharmacology
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Embryonic and Fetal Development*
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Endothelium, Vascular / embryology
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Fas-Associated Death Domain Protein
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Female
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Gene Expression
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Gene Targeting
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Heart / embryology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Mutation
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Oncogenes
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / physiology
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Signal Transduction
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Tumor Necrosis Factor-alpha / pharmacology
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fas Receptor / genetics
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fas Receptor / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Fadd protein, mouse
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Fas-Associated Death Domain Protein
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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fas Receptor
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Doxorubicin