XBP1 induces WFS1 through an endoplasmic reticulum stress response element-like motif in SH-SY5Y cells
XBP1 induces WFS1 through an endoplasmic reticulum stress response element-like motif in SH-SY5Y cells
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DOI：
10.1111/j.1471-4159.2006.03772.x
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发表时间：
2006-04-01
影响因子：
4.7
通讯作者：
Kato, T
中科院分区：
文献类型：
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作者：
Kakiuchi, C;Ishiwata, M;Kato, T
XBP1 是内质网 (ER) 应激反应途径中的关键转录因子。在之前的一项研究中，我们提出 XBP1 与双相情感障碍之间可能存在联系，但其在神经元细胞中的作用尚未阐明。在这里，我们使用表达 XBP1 的载体转染的 SH-SY5Y 细胞中的 DNA 微阵列分析检查了 XBP1 的靶基因。在 XBP1 上调的基因中，观察到最显着的 p 值是 WFS1，它是一种 ER 应激反应相关基因。检查 WFS1 的启动子区域，我们发现了一个与 ER 应激反应元件 (ERSE) 高度相似的保守序列 (CGAGGCGCACCGTGATTGG)。启动子测定表明，这种 ERSE 样基序对于 XBP1 对 WFS1 的调节至关重要。电泳迁移率变动分析表明 XBP1 不直接结合该序列。我们的结果表明 WFS1 是 SH-SY5Y 细胞中 XBP1 的靶基因之一。
XBP1 is a key transcription factor in the endoplasmic reticulum ( ER) stress response pathway. In a previous study, we suggested a possible link between XBP1 and bipolar disorder, but its role in neuronal cells has not yet been clarified. Here we examined the target genes of XBP1, using DNA microarray analysis in SH-SY5Y cells transfected with an XBP1-expressing vector. Among the genes up-regulated by XBP1, the most significant p-value was observed for WFS1, which is an ER stress response-related gene. Examining the promoter region of WFS1, we found a conserved sequence (CGAGGCGCACCGTGATTGG) that is highly similar to the ER stress response element (ERSE). A promoter assay showed that this ERSE-like motif is critical for the regulation of WFS1 by XBP1. An electrophoretic mobility shift assay suggested that XBP1 does not directly bind to this sequence. Our results demonstrate that WFS1 is one of the target genes of XBP1 in SH-SY5Y cells.