Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors.
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.
Chen
Nien-Jung
NJ
The Campbell Family Institute for Breast Cancer Research, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1.
Chio
Iok In Christine
II
Lin
Wen-Jye
WJ
Duncan
Gordon
G
Chau
Hien
H
Katz
David
D
Huang
Huey-Lan
HL
Pike
Kelly A
KA
Hao
Zhenyue
Z
Su
Yu-Wen
YW
Yamamoto
Kazuo
K
de Pooter
Renée F
RF
Zúñiga-Pflücker
Juan Carlos
JC
Wakeham
Andrew
A
Yeh
Wen-Chen
WC
Mak
Tak W
TW
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
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