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在未折叠蛋白反应的适应阶段调节 X 盒结合蛋白 1(XBP1)的表达。

modulates X-box-binding protein 1 (XBP1) expression during the adaptive phase of the unfolded protein response.

机构信息

Department of Inorganic Chemistry, Medical University of Gdansk, Gdansk, Poland.

Laboratory of Bioinformatics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.

出版信息

FASEB J. 2019 Oct;33(10):11541-11554. doi: 10.1096/fj.201900600RR. Epub 2019 Jul 17.

Abstract

During endoplasmic reticulum (ER) stress conditions, an adaptive signaling network termed the unfolded protein response (UPR) is activated. The UPR's function is to increase ER protein-folding capacity in order to attenuate ER stress, restore ER homeostasis, and, most importantly, promote cell survival. X-box-binding protein 1 (XBP1) is one component of the UPR and is a proadaptive transcription factor that is subject to transcriptional, post-transcriptional, and post-translational control. In the present study, we identified a post-transcriptional mechanism mediated by that governs the expression of both the spliced (active) and unspliced (latent) forms of mRNAs. We showed that directly attenuates spliced XBP1 () mRNA levels during ER stress and thus regulates the proadaptive component of the UPR that is mediated by XBP1s without interfering with the induction of apoptotic responses.-Bartoszewska, S., Cabaj, A., Dąbrowski, M., Collawn, J. F., Bartoszewski, R. modulates X-box-binding protein 1 (XBP1) expression during the adaptive phase of the unfolded protein response.

摘要

在内质网(ER)应激条件下,一种称为未折叠蛋白反应(UPR)的适应性信号网络被激活。UPR 的功能是增加 ER 蛋白折叠能力,以减轻 ER 应激,恢复 ER 稳态,最重要的是促进细胞存活。X 盒结合蛋白 1(XBP1)是 UPR 的一个组成部分,是一种促适应性转录因子,受到转录、转录后和翻译后控制。在本研究中,我们确定了一种由介导的转录后机制,该机制调节 XBP1 mRNA 的剪接(活性)和未剪接(潜伏)形式的表达。我们表明,在 ER 应激期间,直接下调剪接的 XBP1()mRNA 水平,从而调节 XBP1s 介导的 UPR 的促适应性成分,而不干扰凋亡反应的诱导。-Bartoszewska,S.,Cabaj,A.,Dąbrowski,M.,Collawn,J. F.,Bartoszewski,R. 在未折叠蛋白反应的适应性阶段调节 X 盒结合蛋白 1(XBP1)的表达。

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