一个依赖于SUMOylation的途径通过PPAR-gamma调节了炎症反应基因的转抑制
Gabriel Pascual1, Amy L Fong, Sumito Ogawa
1Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature
|August 30, 2005
概括
过氧体增殖器激活受体-玛 (PPAR-玛) 激动剂通过招募核心抑制剂来向基因促进体来抑制炎症基因. 这种机制解释了PPAR-gamma如何从激活剂转化为抑制剂,从而影响免疫力和平衡.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 过酶增殖器激活受体- (PPAR-) 对于脂肪生成和葡萄糖稳定至关重要,被胰岛素敏感药物向.
- 通过核因子卡帕B (NF-kappaB) 转抑制的PPAR-马激动剂的抗炎作用与抗糖尿病和抗动脉原生作用有关,但在机理上尚不清楚.
研究的目的:
- 阐明PPAR-gamma抑制小鼠巨细胞中炎症基因转录的分子途径.
- 确定参与PPAR-gamma介导基因抑制的初始步骤和关键分子参与者.
主要方法:
- 研究了PPAR-gamma连接体结合域的依赖连接体的SUMOylation.
- 研究了PPAR-gamma对核受体核心抑制剂 (NCoR) - 希斯脱乙酶-3 (HDAC3) 复合物的向在炎症基因促进器上.
- 评估了对无处不在/19S蛋白酶体机械和核心压缩机复合物去除的招募的影响.
主要成果:
- 结合体的PPAR-马经历SUMOylation,将其向炎症基因促进者的NCoR-HDAC3复合体.
- 这种招募阻止了无处不在的/19S蛋白酶体机械去除核心压缩复合体.
- 因此,NCoR复合体仍然结合,保持目标基因处于抑制状态.
结论:
- 一个新的途径揭示了抗激素结合的PPAR-gamma如何作为NF-kappaB目标基因的促销器特异抑制剂.
- 这种机制解释了PPAR-gamma从转录激活剂转化为抑制剂的转化.
- 这些发现提供了关于PPAR-gamma.gamma对免疫和恒温的调节的见解.
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