title: TRADD interacts with STAT1-alpha and influences interferon-gamma signaling.
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.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Duane R
authors.initials: DR
authors.lastname: Wesemann
authors.forename: Hongwei
authors.initials: H
authors.lastname: Qin
authors.forename: Natalia
authors.initials: N
authors.lastname: Kokorina
authors.forename: Etty N
authors.initials: EN
authors.lastname: Benveniste
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D034622:RNA Interference; D015398:Signal Transduction / Q000276:immunology; D053199:TNF Receptor-Associated Death Domain Protein; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
chemical_list: D002352:Carrier Proteins; D050832:Interferon-Stimulated Gene Factor 3; D053199:TNF Receptor-Associated Death Domain Protein; C481226:Tradd protein, mouse; D014157:Transcription Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C079868:gamma interferon activation factor; D007371:Interferon-gamma