A Role for Protein Inhibitor of Activated STAT1 (PIAS1) in Lipogenic Regulation through SUMOylation-independent Suppression of Liver X Receptors
文献类型：期刊论文
| 作者 | Zhang, Yongliang; Gan, Zhenji; Huang, Ping; Zhou, Luting; Mao, Ting; Shao, Mengle; Jiang, Xiaomeng; Chen, Yan（陈雁） ; Ying, hao（应浩）; Cao, Meina
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2012 |
| 卷号 | 287期号:45页码:37973-37985 |
| 英文摘要 | Liver X receptors (LXRs) are nuclear receptors that function to modulate lipid metabolism as well as immune and inflammatory responses. Upon activation by their ligands, LXRs up-regulate a spectrum of gene transcription programs involved in cholesterol and fatty acid homeostasis. However, the mechanisms by which LXR-mediated transcriptional activation is regulated remain incompletely understood. Here, we show that PIAS1, a member of the protein inhibitor of the activated STAT family of proteins with small ubiquitin-like modifier (SUMO) E3 ligase activity, acts to suppress LXR ligand-dependent transcriptional activation of the lipogenic program in hepatocytes. We found that liver mRNA expression levels of Pias1 and Pias3 were inversely associated with those of genes involved in lipogenesis in mouse models with diet-induced or genetic obesity. Overexpression of PIAS1 in primary hepatocytes resulted in a reduction of LXR ligand-induced fatty acid synthesis and suppression of the expression of lipogenic genes, including Srebp1c and Fas. Moreover, PIAS1 was able to interact with LXR beta and repress its transcriptional activity upon ligand stimulation, which did not require PIAS1-promoted SUMO modification of LXR beta. In addition, PIAS1 could also interact with PGC-1 beta and attenuate its association with LXR beta, blunting the ability of PGC-1 beta to co-activate LXR beta. Importantly, PIAS1 impaired LXR beta binding to its target DNA sequence. Taken together, our results suggest that PIAS1 may serve as a lipogenic regulator by negatively modulating LXRs in a SUMOylation-independent manner. |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | THYROID-HORMONE RECEPTOR ; ORPHAN NUCLEAR RECEPTORS ; FATTY-ACID SYNTHESIS ; LXR-ALPHA ; TRANSCRIPTIONAL REGULATION ; MEDIATES TRANSREPRESSION ; HEPATIC LIPOGENESIS ; RESPONSE PATHWAY ; GENE-ACTIVATION ; PPAR-GAMMA |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000310642200032 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/65]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 中国科学院上海生命科学研究院营养科学研究所_营养与代谢性疾病中的基因表达调控研究组 |
| 推荐引用方式 GB/T 7714 | Zhang, Yongliang,Gan, Zhenji,Huang, Ping,et al. A Role for Protein Inhibitor of Activated STAT1 (PIAS1) in Lipogenic Regulation through SUMOylation-independent Suppression of Liver X Receptors[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(45):37973-37985. |
| APA | Zhang, Yongliang.,Gan, Zhenji.,Huang, Ping.,Zhou, Luting.,Mao, Ting.,...&Liu, Yong.(2012).A Role for Protein Inhibitor of Activated STAT1 (PIAS1) in Lipogenic Regulation through SUMOylation-independent Suppression of Liver X Receptors.JOURNAL OF BIOLOGICAL CHEMISTRY,287(45),37973-37985. |
| MLA | Zhang, Yongliang,et al."A Role for Protein Inhibitor of Activated STAT1 (PIAS1) in Lipogenic Regulation through SUMOylation-independent Suppression of Liver X Receptors".JOURNAL OF BIOLOGICAL CHEMISTRY 287.45(2012):37973-37985. |
入库方式： OAI收割
来源：上海营养与健康研究所
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