203 663

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

Authors
Lee, JH  | Kim, H | Park, SJ  | Woo, JH  | Joe, EH  | Jou, I
Citation
Science signaling, 9(439). : ra78-ra78, 2016
Journal Title
Science signaling
ISSN
1945-08771937-9145
Abstract
Liver 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.
MeSH

DOI
10.1126/scisignal.aaf4850
PMID
27485016
Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
박, 수정  |  우, 주홍  |  이, 지훈  |  조, 은혜  |  주, 일로
Files in This Item:
27485016.pdfDownload
Export

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

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

Browse