Abstract
Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is essential in recruiting signaling molecules to the TNFR1 receptor complex. Interferon-gamma (IFN-gamma) is a potent activator of macrophages and uses signal transducer and activator of transcription 1-alpha (STAT1-alpha) for signal transduction. Here we demonstrate that IFN-gamma induces the formation of a nuclear-localized TRADD-STAT1-alpha complex. IFN-gamma-mediated STAT1-alpha phosphorylation was prolonged in cells with reduced TRADD expression. Moreover, we noted an increase in IFN-gamma-mediated STAT1-alpha DNA-binding activity, nuclear presence and transcriptional potential in the TRADD knockdown cells. These data indicate that TRADD may be involved in IFN-gamma signaling by forming a complex with STAT1-alpha within the nucleus and regulating IFN-gamma-mediated STAT1-alpha activation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Active Transport, Cell Nucleus
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Animals
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Binding Sites
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / immunology*
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Carrier Proteins / metabolism
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Cell Line
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Gene Expression Regulation
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Interferon-Stimulated Gene Factor 3
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Interferon-gamma / metabolism*
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Macrophage Activation
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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RNA Interference
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Signal Transduction / immunology
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TNF Receptor-Associated Death Domain Protein
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription Factors / metabolism
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Transcription, Genetic
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins*
Substances
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Carrier Proteins
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Interferon-Stimulated Gene Factor 3
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TNF Receptor-Associated Death Domain Protein
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Tradd protein, mouse
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Transcription Factors
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
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gamma interferon activation factor
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Interferon-gamma