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Title 

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

Authors 

J M YukD M ShinH M LeeJ J KimS W KimH S JinC S YangK A ParkD ChandaD K KimS M HuangS K LeeChul Ho LeeJ M KimC H SongS Y LeeG M HurD D MooreH S ChoiE K Jo

Publisher 

Nature Publishing Group

Issue Date 

2011

Citation 

Nature Immunology, vol. 12, no. 8, pp. 742-751

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

Link 

http://dx.doi.org/10.1038/ni.2064

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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