Negative regulation of Toll-like receptor signaling by NF-κB p50 ubiquitination blockade
Negative regulation of Toll-like receptor signaling by NF-κB p50 ubiquitination blockade
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DOI：
10.1126/science.1142953
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发表时间：
2007-08-03
期刊：
影响因子：
56.9
通讯作者：
Chen, Youhai H.
中科院分区：
文献类型：
--
作者：
Carmody, Ruaidhri J.;Ruan, Qingguo;Chen, Youhai H.
Toll-like receptors (TLRs) trigger the production of inflammatory cytokines and shape adaptive and innate immunity to pathogens. We report the identification of B cell leukemia (Bcl)-3 as an essential negative regulator of TLR signaling. By blocking ubiquitination of p50, a member of the nuclear factor (NF)-kB family, Bcl-3 stabilizes a p50 complex that inhibits gene transcription. As a consequence, Bcl-3-deficient mice and cells were found to be hypersensitive to TLR activation and unable to control responses to lipopolysaccharides. Thus, p50 ubiquitination blockade by Bcl-3 limits the strength of TLR responses and maintains innate immune homeostasis. These findings indicate that the p50 ubiquitination pathway can be selectively targeted to control deleterious inflammatory diseases.
