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

Title
The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors
Authors
Yuk J.-M.Shin D.-M.Lee H.-M.Kim J.-J.Kim S.-W.Jin H.S.Yang C.-S.Park K.A.Chanda D.Kim D.-K.Huang S.M.Lee S.K.Lee C.-H.Kim J.-M.Song C.-H.Lee S.Y.Hur G.M.Moore D.D.Choi H.-S.Jo E.-K.
Ewha Authors
이수영
SCOPUS Author ID
이수영scopus
Issue Date
2011
Journal Title
Nature Immunology
ISSN
1529-2908JCR Link
Citation
vol. 12, no. 8, pp. 742 - 751
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2011 Nature America, Inc. All rights reserved.
DOI
10.1038/ni.2064
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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