| First Author | Yuk JM | Year | 2011 |
| Journal | Nat Immunol | Volume | 12 |
| Issue | 8 | Pages | 742-51 |
| PubMed ID | 21725320 | Mgi Jnum | J:174433 |
| Mgi Id | MGI:5086034 | Doi | 10.1038/ni.2064 |
| Citation | Yuk JM, et al. (2011) The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors. Nat Immunol 12(8):742-51 |
| abstractText | 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-kappaB signaling pathway, acting as both a repressor of transactivation of the NF-kappaB 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. |
