Endoplasmic reticulum (ER) stress responses have been demonstrated to play important roles in maintaining various cellular functions and to underlie many tissue dysfunctions. In this study, we identified Sec16B as an ER stress-inducible gene by microarray analysis of brefeldin A (BFA)-inducible genes in a mouse neuroblastoma cell-line, Neuro2a. Sec16B mRNA was induced by treatment with the ER stress-inducing reagents thapsigargin (Tg) and brefeldin A in a time-dependent manner. In the genomic sequence of the mouse Sec16B gene, we found an unfolded protein response element (UPRE), which is well conserved between humans and mice. Using luciferase reporter analyses, we showed that the UPRE in the mouse Sec16B gene was functional and responded well to ER stress-inducing stimuli and spliced XBP1 (sXBP1)-overexpression. In addition, a unique ATF4-responsive sequence within the first intron of the mouse Sec16B gene was characterized. Our study may help to elucidate the regulation of trafficking through the ER-Golgi apparatus and the biogenesis of ER-derived intracellular organelles.

中文翻译：

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Neuro2a 细胞中内质网应激诱导基因 Sec16B 的转录调控。

内质网 (ER) 应激反应已被证明在维持各种细胞功能方面发挥重要作用，并且是许多组织功能障碍的基础。在这项研究中，我们通过对小鼠神经母细胞瘤细胞系 Neuro2a 中 brefeldin A (BFA) 诱导基因的微阵列分析，将 Sec16B 鉴定为内质网应激诱导基因。Sec16B mRNA 是由内质网应激诱导试剂毒胡萝卜素 (Tg) 和布雷菲尔德菌素 A 以时间依赖性方式诱导的。在小鼠 Sec16B 基因的基因组序列中，我们发现了一个未折叠蛋白反应元件 (UPRE)，它在人和小鼠之间非常保守。使用荧光素酶报告基因分析，我们发现小鼠 Sec16B 基因中的 UPRE 是有功能的，并且对内质网应激诱导刺激和剪接 XBP1 (sXBP1) 过度表达反应良好。此外，表征了小鼠 Sec16B 基因第一个内含子内独特的 ATF4 响应序列。我们的研究可能有助于阐明通过 ER-高尔基体的运输调节和 ER 衍生的细胞内细胞器的生物发生。