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Title: The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors.

Authors: 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; Jo, Eun-Kyeong

Published In Nat Immunol, (2011 Jul 03)

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-κB signaling pathway, acting as both a repressor of transactivation of the NF-κB 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.

PubMed ID: 21725320 Exiting the NIEHS site

MeSH Terms: AMP-Activated Protein Kinases/immunology; Animals; Chromatin Immunoprecipitation; Female; Immunoblotting; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B/immunology*; Receptors, Cytoplasmic and Nuclear/immunology*; Sepsis/immunology*; Signal Transduction; TNF Receptor-Associated Factor 6/immunology; Toll-Like Receptors/immunology*; Ubiquitination/immunology

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