XBP1 activates the transcription of its target genes via an ACGT core sequence under ER stress
XBP1 activates the transcription of its target genes via an ACGT core sequence under ER stress
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DOI：
10.1016/j.bbrc.2005.04.039
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发表时间：
2005-06-17
影响因子：
3.1
通讯作者：
Imaizumi, K
中科院分区：
文献类型：
--
作者：
Kanemoto, S;Kondo, S;Imaizumi, K
在哺乳动物中，跨膜蛋白激酶/核糖核酸内切酶IRE 1被内质网应激激活，随后加工XBP 1 mRNA以产生活性形式的XBP 1蛋白。剪接形式的XBP 1蛋白作为转录因子，并诱导ER驻留分子伴侣的表达。然而，在内质网应激过程中，XBP 1如何促进其靶基因的转录以及XBP 1的顺式作用元件的机制尚不清楚。最近的研究表明，DnaJ家族成员MDG 1/ERdj 4的表达受IRE 1-XBP 1通路的调控。在本报告中，我们调查的MDG 1/ERdj 4基因表达的调控机制，由XBP 1。我们确定了MDG 1/ERdj 4启动子区域的顺式作用元件，其中XBP 1特异性结合响应ER应激。我们的研究结果揭示了ER应激条件下IRE 1-XBP 1通路的靶序列。(c)2005年爱思唯尔公司All rights reserved.
In mammals, the transmembrane protein kinase/endoribonuclease IRE1 is activated by endoplasmic reticulum stress and subsequently processes XBP1 mRNA to generate an active form of XBP1 protein. The spliced form of XBP1 protein acts as a transcription factor and induces the expression of ER-resident molecular chaperones. However, the mechanism for how XBP1 promotes the transcription of its target genes as well as the cis-acting elements for XBP1 during ER stress has been unclear. Recently, it was demonstrated that the expression of MDG1/ERdj4, a member of the DnaJ family, is regulated by the IRE1-XBP1 pathway. In the present report, we investigated the regulatory mechanisms of MDG1/ERdj4 gene expression by XBP1. We identified a cis-acting element in the MDG1/ERdj4 promoter region, to which XBP1 specifically binds in response to ER stress. Our results reveal a target sequence for the IRE1-XBP1 pathway under ER stress conditions. (c) 2005 Elsevier Inc. All rights reserved.