title: Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors.
abstract: Tumor necrosis factor receptor 1-associated death domain protein (TRADD) is the core adaptor recruited to TNF receptor 1 (TNFR1) upon TNFalpha stimulation. In cells from TRADD-deficient mice, TNFalpha-mediated apoptosis and TNFalpha-stimulated NF-kappaB, JNK, and ERK activation are defective. TRADD is also important for germinal center formation, DR3-mediated costimulation of T cells, and TNFalpha-mediated inflammatory responses in vivo. TRADD deficiency does not enhance IFNgamma-induced signaling. Importantly, TRADD has a novel role in TLR3 and TLR4 signaling. TRADD participates in the TLR4 complex formed upon LPS stimulation, and TRADD-deficient macrophages show impaired cytokine production in response to TLR ligands in vitro. Thus, TRADD is a multifunctional protein crucial both for TNFR1 signaling and other signaling pathways relevant to immune responses.
authors: The Campbell Family Institute for Breast Cancer Research, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1.
authors: Nien-Jung
authors: NJ
authors: Chen
authors: Iok In Christine
authors: II
authors: Chio
authors: Wen-Jye
authors: WJ
authors: Lin
authors: Gordon
authors: G
authors: Duncan
authors: Hien
authors: H
authors: Chau
authors: David
authors: D
authors: Katz
authors: Huey-Lan
authors: HL
authors: Huang
authors: Kelly A
authors: KA
authors: Pike
authors: Zhenyue
authors: Z
authors: Hao
authors: Yu-Wen
authors: YW
authors: Su
authors: Kazuo
authors: K
authors: Yamamoto
authors: Renée F
authors: RF
authors: de Pooter
authors: Juan Carlos
authors: JC
authors: Zúñiga-Pflücker
authors: Andrew
authors: A
authors: Wakeham
authors: Wen-Chen
authors: WC
authors: Yeh
authors: Tak W
authors: TW
authors: Mak
mesh_terms: D000818:Animals; D017209:Apoptosis; D018858:Germinal Center; D007249:Inflammation; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes; D053199:TNF Receptor-Associated Death Domain Protein / Q000378:metabolism* / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; C519703:TLR3 protein, mouse; D053199:TNF Receptor-Associated Death Domain Protein; C493487:Tlr4 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha