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

Cited 139 time in scopus
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Title
The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors
Author(s)
J M Yuk; D M Shin; H M Lee; J J Kim; S W Kim; H S Jin; C S Yang; K A Park; D Chanda; D K Kim; S M Huang; S K Lee; Chul Ho Lee; J M Kim; C H Song; S Y Lee; G M Hur; D D Moore; H S Choi; E K Jo
Bibliographic Citation
Nature Immunology, vol. 12, no. 8, pp. 742-751
Publication Year
2011
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.
ISSN
1529-2908
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/ni.2064
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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