title: The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors.
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.
authors: Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea.
authors: Jae-Min
authors: JM
authors: Yuk
authors: Dong-Min
authors: DM
authors: Shin
authors: Hye-Mi
authors: HM
authors: Lee
authors: Jwa-Jin
authors: JJ
authors: Kim
authors: Sun-Woong
authors: SW
authors: Kim
authors: Hyo Sun
authors: HS
authors: Jin
authors: Chul-Su
authors: CS
authors: Yang
authors: Kyeong Ah
authors: KA
authors: Park
authors: Dipanjan
authors: D
authors: Chanda
authors: Don-Kyu
authors: DK
authors: Kim
authors: Song Mei
authors: SM
authors: Huang
authors: Sang Ki
authors: SK
authors: Lee
authors: Chul-Ho
authors: CH
authors: Lee
authors: Jin-Man
authors: JM
authors: Kim
authors: Chang-Hwa
authors: CH
authors: Song
authors: Soo Young
authors: SY
authors: Lee
authors: Gang Min
authors: GM
authors: Hur
authors: David D
authors: DD
authors: Moore
authors: Hueng-Sik
authors: HS
authors: Choi
authors: Eun-Kyeong
authors: EK
authors: Jo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000276:immunology; D000818:Animals; D047369:Chromatin Immunoprecipitation; D005260:Female; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D054875:Ubiquitination / Q000276:immunology
chemical_list: D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; C099713:nuclear receptor subfamily 0, group B, member 2; D055372:AMP-Activated Protein Kinases