标题:The IRE1 alpha-XBP1 pathway regulates metabolic stress-induced compensatory proliferation of pancreatic beta-cells
作者:Xu, Tongfu; Yang, Liu; Yan, Cheng; Wang, Xiaoxia; Huang, Ping; Zhao, Feng; Zhao, Liyun; Zhang, Mingliang; Jia, Weiping; Wang, Xiangd 更多
作者机构:[Xu Tongfu] Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong 250012, China.;[Wang Xiangdong] Department of Cell Bio 更多
通讯作者地址:[Liu, Y]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China.
来源:细胞研究
出版年:2014
卷:24
期:9
页码:1137-1140
DOI:10.1038/cr.2014.55
摘要:In eukaryotes, increased protein folding demand at the endoplasmic reticulum (ER) activates the unfolded protein response (UPR), which plays a pivotal role in control of cellular functions and survival under ER stress. Chronic ER stress is thought to contribute to the pathogenic progression of diabetes. Inositol-requiring enzyme 1 (IRE1), an ER-resident transmembrane Ser/Thr protein kinase and endoribonuclease, is the most conserved ER stress sensor that mediates a key branch of the UPR. In mammals, activation of IRE1alpha results in non-conventional splicing of the mRNA encoding the transcription factor X-box binding protein 1 (XBP1), generating a spliced active form of XBP1 (XBP1s) to initiate a major UPR program. The IRE1-XBP1 pathway has been implicated in the homeostatic regulation of pancreatic islet beta-cells. Whereas glucose-stimulated IRE1alpha activation is coupled to insulin production, IRE1alpha also degrades insulin mRNAs under severe ER stress conditions. Interestingly, genetic deletion of XBP1 in beta-cells of mice was reported to result in a feedback hyperactivation of IRE1alpha, causing defective proinsulin processing and insulin secretion. However, the precise role in vivo of IRE1alpha in integrating metabolic ER stress signals to regulate beta-cell functions remains largely elusive.
收录类别:CSCD;SCIE
WOS核心被引频次:14
资源类型:期刊论文
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