1. The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors.
- Author
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Yuk, Jae-Min, Shin, Dong-Min, Lee, Hye-Mi, Kim, Jwa-Jin, Kim, Sun-Woong, Jin, Hyo Sun, Yang, Chul-Su, Park, Kyeong Ah, Chanda, Dipanjan, Kim, Don-Kyu, Huang, Song Mei, Lee, Sang Ki, Lee, Chul-Ho, Kim, Jin-Man, Song, Chang-Hwa, Lee, Soo Young, Hur, Gang Min, Moore, David D, Choi, Hueng-Sik, and Jo, Eun-Kyeong
- Subjects
NUCLEAR receptors (Biochemistry) ,PROTEINS ,CELLULAR signal transduction ,METABOLIC regulation ,NF-kappa B ,PROTEIN kinases ,GENE expression ,CELLULAR control mechanisms - Abstract
The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxin-induced sepsis. SHP had dual regulatory functions in a canonical transcription factor NF-?B signaling pathway, acting as both a repressor of transactivation of the NF-?B subunit p65 and an inhibitor of polyubiquitination of the adaptor TRAF6. SHP-mediated inhibition of signaling via the TLR was mimicked by macrophage-stimulating protein (MSP), a strong inducer of SHP expression, via an AMP-activated protein kinase-dependent signaling pathway. Our data identify a previously unrecognized role for SHP in the regulation of TLR signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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