The promoter of cell growth- and RNA protection-associated SND1 gene is activated by endoplasmic reticulum stress in human hepatoma cells.

The promoter of cell growth- and RNA protection-associated SND1 gene is activated by endoplasmic reticulum stress in human hepatoma cells.
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DOI:
10.1186/s12858-014-0025-2
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发表时间:
2014-12-11
期刊:
影响因子:
--
通讯作者:
Martínez MJ
Martínez MJ
中科院分区:
生物4区
文献类型:
--
作者:
Armengol S;Arretxe E;Enzunza L;Mula S;Ochoa B;Chico Y;Martínez MJ

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葡萄球菌含核酸酶结构域蛋白1(SND 1)参与基因表达调控和RNA保护。虽然许多研究已经确定SND 1蛋白表达受到与肿瘤生长、缺氧、炎症、热休克和氧化条件相关的细胞应激的调节,但对负责SND 1表达的因素知之甚少。在这里,我们已经接近这个问题,通过分析人SND 1基因的转录反应的药理内质网(ER)的压力在肝癌细胞。我们提供的第一个证据表明,SND 1启动子活性增加,在人类肝癌细胞暴露于毒胡萝卜素或衣霉素或异位表达的ATF 6,一个关键的转录因子在未折叠的蛋白质反应触发的ER压力。SND 1启动子5 '侧翼区的缺失分析表明,在片段(-934,+221)中激活最大,该片段包含了近端启动子中大部分预测的ER应激反应元件。定量实时PCR显示SND 1 mRNA表达增加近3倍的应力诱导剂,而SND 1蛋白最大上调(3.4倍)暴露于衣霉素,蛋白糖基化抑制剂的细胞。人肝癌细胞中细胞生长和RNA保护相关SND 1基因的启动子活性受ER应激的上调
Staphyloccocal nuclease domain-containing protein 1 (SND1) is involved in the regulation of gene expression and RNA protection. While numerous studies have established that SND1 protein expression is modulated by cellular stresses associated with tumor growth, hypoxia, inflammation, heat-shock and oxidative conditions, little is known about the factors responsible for SND1 expression. Here, we have approached this question by analyzing the transcriptional response of human SND1 gene to pharmacological endoplasmic reticulum (ER) stress in liver cancer cells. We provide first evidence that SND1 promoter activity is increased in human liver cancer cells upon exposure to thapsigargin or tunicamycin or by ectopic expression of ATF6, a crucial transcription factor in the unfolded protein response triggered by ER stress. Deletion analysis of the 5’-flanking region of SND1 promoter identified maximal activation in fragment (-934, +221), which contains most of the predicted ER stress response elements in proximal promoter. Quantitative real-time PCR revealed a near 3 fold increase in SND1 mRNA expression by either of the stress-inducers; whereas SND1 protein was maximally upregulated (3.4-fold) in cells exposed to tunicamycin, a protein glycosylation inhibitor. Promoter activity of the cell growth- and RNA-protection associated SND1 gene is up-regulated by ER stress in human hepatoma cells.
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