Differential SUMOylation of LXRα and LXRβ Mediates Transrepression of STAT1 Inflammatory Signaling in IFN-γ-Stimulated Brain Astrocytes

被引：136

作者：

Lee, Jee Hoon ^{[1
,2
]}

Park, Sang Myun ^{[1
,2
]}

Kim, Ohn Soon ^{[1
,2
]}

Lee, Chang Seok ^{[1
,2
]}

Woo, Joo Hong ^{[1
,2
]}

Park, Soo Jung ^{[1
,2
]}

Joe, Eun-hye ^{[1
,2
]}

Jou, Ilo ^{[1
,2
]}

机构：

[1] Ajou Univ, Sch Med, Dept Pharmacol, Suwon 442721, South Korea

[2] Ajou Univ, Sch Med, Chron Inflammatory Dis Res Ctr, Suwon 442721, South Korea

来源：

MOLECULAR CELL | 2009年 / 35卷 / 06期

关键词：

LIVER-X-RECEPTOR; ALZHEIMERS-DISEASE; MOUSE MODEL; HISTONE DEACETYLASES; NUCLEAR RECEPTORS; LIPID-METABOLISM; GENE-EXPRESSION; PIAS PROTEINS; PPAR-GAMMA; ACTIVATION;

D O I：

10.1016/j.molcel.2009.07.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To unravel the roles of LXRs in inflammation and immunity, we examined the function of LXRs in development of IFN-gamma-mediated inflammation using cultured rat brain astrocytes. LXR ligands inhibit neither STAT1 phosphorylation nor STAT1 translocation to the nucleus but, rather, inhibit STAT1 binding to promoters and the expression of IRF1, TNF alpha, and IL-6, downstream effectors of STAT1 action. Immunoprecipitation data revealed that LXR beta formed a trimer with PIAS1-pSTAT1, whereas LXR alpha formed a trimer with HDAC4-pSTAT1, mediated by direct ligand binding to the LXR proteins. In line with the fact that both PIAS1 and HDAC4 belong to the SUMO E3 ligase family, LXR beta and LXR alpha were SUMO-conjugated by PIAS1 or HDAC4, respectively, and SUMOylation was blocked by transient transfection of appropriate individual siRNAs, reversing LXR-induced suppression of IRF1 and TNF alpha expression. Together, our data show that SUMOylation is required for the suppression of STAT1-dependent inflammatory responses by LXRs in IFN-gamma-stimulated brain astrocytes.

引用

页码：806 / 817

页数：12

共 36 条

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