Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors

Nien Jung Chen, Iok In Christine Chio, Wen Jye Lin, Gordon Duncan, Hien Chau, David Katz, Huey Lan Huang, Kelly A. Pike, Zhenyue Hao, Yu Wen Su, Kazuo Yamamoto, Renée F. De Pooter, Juan Carlos Zúñiga-Pflücker, Andrew Wakeham, Wen Chen Yeh, Tak W. Mak

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Tumor necrosis factor receptor 1-associated death domain protein (TRADD) is the core adaptor recruited to TNF receptor 1 (TNFR1) upon TNFα stimulation. In cells from TRADD-deficient mice, TNFα-mediated apoptosis and TNFα-stimulated NF-κB, JNK, and ERK activation are defective. TRADD is also important for germinal center formation, DR3-mediated costimulation of T cells, and TNFα-mediated inflammatory responses in vivo. TRADD deficiency does not enhance IFNγ-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.

Original languageEnglish
Pages (from-to)12429-12434
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
StatePublished - 26 Aug 2008


  • Innate immunity
  • TNF


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