ER stress signaling by regulated proteolysis of ATF6
ER stress signaling by regulated proteolysis of ATF6
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DOI：
10.1016/j.ymeth.2004.10.011
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发表时间：
2005-04-01
期刊：
影响因子：
4.8
通讯作者：
Prywes, R
中科院分区：
文献类型：
--
作者：
Shen, JS;Prywes, R
ATF6是内质网（ER）膜锚定转录因子，在内质网应激反应中被膜内蛋白水解激活。内质网应激时，ATF6从内质网转运到高尔基体，由位点1和位点2蛋白酶进行加工。贩卖是由ER伴侣BiP/GRP78控制的。在这里. .我们描述了我们用来研究组织培养细胞中ATF6调节的实验方法。这些方法被用来研究ATF6在内质网应激反应中激活的几个关键步骤，包括BiP与ATF6的结合和解离，从内质网到高尔基体的易位和高尔基体的裂解。此外，荧光素酶报告基因检测是监测内质网应激和ATF6激活的灵敏方法。这些方法不仅有助于研究ATF6和内质网应激反应，还可能有助于阐明内质网应激反应在许多涉及错误折叠蛋白质的人类疾病中的作用，以及在需要更高内质网折叠能力的分泌组织的分化中所起的作用。(c) 2004 Elsevier Inc.版权所有。
ATF6 is an endoplasmic reticulum (ER) membrane-anchored transcription factor activated by intramembrane proteolysis in the ER stress response. Upon ER stress, ATF6 is transported from the ER to the Golgi to be processed by site-1 and site-2 proteases. The trafficking is controlled by the ER chaperone BiP/GRP78. Here.. we describe the experimental methods that we have used to study ATF6 regulation in tissue culture cells. These methods were used to investigate several key steps of ATF6 activation in the ER stress response including binding and dissociation of BiP to ATF6, translocation from the ER to the Golgi and cleavage in the Golgi. In addition, luciferase reporter assays were a sensitive way to monitor ER stress and ATF6 activation. These methods were not only useful for the study of ATF6 and the ER stress response, they might also help to elucidate the roles of the ER stress response in a number of human diseases involving misfolded proteins and in the differentiation of secretory tissues which require higher ER folding capacities. (c) 2004 Elsevier Inc. All rights reserved.