Palmitate increases Nur77 expression by modulating ZBP89 and Sp1 binding to the Nur77 proximal promoter in pancreatic β-cells
Palmitate increases Nur77 expression by modulating ZBP89 and Sp1 binding to the Nur77 proximal promoter in pancreatic β-cells
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DOI：
10.1016/j.febslet.2013.10.024
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发表时间：
2013-11-29
期刊：
影响因子：
3.5
通讯作者：
Helleboid-Chapman, Audrey
中科院分区：
文献类型：
--
作者：
Mazuy, Claire;Ploton, Maheul;Helleboid-Chapman, Audrey
Nur 77是胰腺β细胞中的应激传感器，其负调节葡萄糖刺激的胰岛素分泌。我们最近表明，β细胞暴露于饱和脂肪酸棕榈酸酯引起的脂毒性休克强烈增加了Nur 77的表达。在这里，使用双荧光素酶报告基因测定和Nur 77启动子缺失构建体，我们鉴定了在翻译起始位点上游-1534和-1512 bp之间的调节盒，其介导Nur 77启动子响应于棕榈酸酯暴露的活化。染色质免疫沉淀，瞬时转染和siRNA介导的敲除试验表明，棕榈酸诱导的Nur 77启动子激活涉及Sp1招聘和ZBP 89从基因启动子释放。(C)2013年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
Nur77 is a stress sensor in pancreatic beta-cells, which negatively regulates glucose-stimulated insulin secretion. We recently showed that a lipotoxic shock caused by exposure of beta- cells to the saturated fatty acid palmitate strongly increases Nur77 expression. Here, using dual luciferase reporter assays and Nur77 promoter deletion constructs, we identified a regulatory cassette between -1534 and -1512 bp upstream from the translational start site mediating Nur77 promoter activation in response to palmitate exposure. Chromatin immunoprecipitation, transient transfection and siRNA-mediated knockdown assays revealed that palmitate induced Nur77 promoter activation involves Sp1 recruitment and ZBP89 release from the gene promoter. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.