Document Detail

The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors.
MedLine Citation:
PMID:  21725320     Owner:  NLM     Status:  MEDLINE    
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.
Jae-Min Yuk; Dong-Min Shin; Hye-Mi Lee; Jwa-Jin Kim; Sun-Woong Kim; Hyo Sun Jin; Chul-Su Yang; Kyeong Ah Park; Dipanjan Chanda; Don-Kyu Kim; Song Mei Huang; Sang Ki Lee; Chul-Ho Lee; Jin-Man Kim; Chang-Hwa Song; Soo Young Lee; Gang Min Hur; David D Moore; Hueng-Sik Choi; Eun-Kyeong Jo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-03
Journal Detail:
Title:  Nature immunology     Volume:  12     ISSN:  1529-2916     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-20     Completed Date:  2011-10-07     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  742-51     Citation Subset:  IM    
Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea.
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MeSH Terms
AMP-Activated Protein Kinases / immunology
Chromatin Immunoprecipitation
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
Reg. No./Substance:
0/NF-kappa B; 0/Receptors, Cytoplasmic and Nuclear; 0/TNF Receptor-Associated Factor 6; 0/Toll-Like Receptors; 0/nuclear receptor subfamily 0, group B, member 2; EC Protein Kinases
Comment In:
Nat Rev Immunol. 2011 Aug;11(8):502   [PMID:  21785453 ]
Nat Immunol. 2011 Aug;12(8):725-7   [PMID:  21772282 ]

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