213 692

Cited 0 times in

Small heterodimer partner SHP mediates liver X receptor (LXR)-dependent suppression of inflammatory signaling by promoting LXR SUMOylation specifically in astrocytes

DC Field Value Language
dc.contributor.authorLee, JH-
dc.contributor.authorKim, H-
dc.contributor.authorPark, SJ-
dc.contributor.authorWoo, JH-
dc.contributor.authorJoe, EH-
dc.contributor.authorJou, I-
dc.date.accessioned2018-05-04T00:26:37Z-
dc.date.available2018-05-04T00:26:37Z-
dc.date.issued2016-
dc.identifier.issn1945-0877-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/15160-
dc.description.abstractLiver X receptors (LXRs) suppress the expression of inflammatory genes in a context-specific manner. In astrocytes, SUMOylation of LXRs promotes their anti-inflammatory effects. We found that small heterodimer partner (SHP), also known as NR0B2 (nuclear receptor subfamily 0, group B, member 2), facilitates the anti-inflammatory actions of LXRs by promoting their SUMOylation. Knockdown of SHP abrogated SUMOylation of LXRs, preventing their anti-inflammatory effects, in primary rat astrocytes but not macrophages. The underlying mechanisms differed according to LXR isoform. SHP promoted SUMO2 and SUMO3 attachment to LXRalpha by interacting directly with the histone deacetylase and E3 SUMO ligase HDAC4. In contrast, SHP promoted SUMO1 attachment to LXRbeta by stabilizing the E3 SUMO ligase PIAS1. SHP bound PIAS1 and disrupted its interaction with the E3 ubiquitin ligase SIAH1. Knocking down SIAH1 rescued LXRbeta SUMOylation in SHP-deficient astrocytes. Our data collectively suggested that SHP mediates the anti-inflammatory actions of LXRs through differential regulation of receptor SUMOylation specifically in astrocytes, thereby revealing potential avenues for therapeutic development in diseases associated with brain inflammation.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAstrocytes/metabolism-
dc.subject.MESHGene Knockdown Techniques-
dc.subject.MESHInflammation/genetics-
dc.subject.MESHInflammation/metabolism-
dc.subject.MESHLiver X Receptors/genetics-
dc.subject.MESHLiver X Receptors/metabolism-
dc.subject.MESHProtein Inhibitors of Activated STAT/genetics-
dc.subject.MESHProtein Inhibitors of Activated STAT/metabolism-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHReceptors, Cytoplasmic and Nuclear/genetics-
dc.subject.MESHReceptors, Cytoplasmic and Nuclear/metabolism-
dc.subject.MESHSignal Transduction-
dc.subject.MESHSumoylation-
dc.titleSmall heterodimer partner SHP mediates liver X receptor (LXR)-dependent suppression of inflammatory signaling by promoting LXR SUMOylation specifically in astrocytes-
dc.typeArticle-
dc.identifier.pmid27485016-
dc.contributor.affiliatedAuthor이, 지훈-
dc.contributor.affiliatedAuthor박, 수정-
dc.contributor.affiliatedAuthor우, 주홍-
dc.contributor.affiliatedAuthor조, 은혜-
dc.contributor.affiliatedAuthor주, 일로-
dc.type.localJournal Papers-
dc.identifier.doi10.1126/scisignal.aaf4850-
dc.citation.titleScience signaling-
dc.citation.volume9-
dc.citation.number439-
dc.citation.date2016-
dc.citation.startPagera78-
dc.citation.endPagera78-
dc.identifier.bibliographicCitationScience signaling, 9(439). : ra78-ra78, 2016-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1937-9145-
dc.relation.journalidJ019450877-
Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Files in This Item:
27485016.pdfDownload

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse