Complementary signaling pathways regulate the unfolded protein response and are required for C-elegans development
Complementary signaling pathways regulate the unfolded protein response and are required for C-elegans development
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DOI：
10.1016/s0092-8674(01)00612-2
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发表时间：
2001-12-28
期刊：
影响因子：
64.5
通讯作者：
Kaufman, RJ
中科院分区：
文献类型：
--
作者：
Shen, XH;Ellis, RE;Kaufman, RJ
未折叠蛋白反应(UPR)是一种转录和翻译的细胞内信号通路，由内质网(ER)管腔内未折叠蛋白的积聚激活。我们已经使用线虫作为遗传模型系统来剖析多细胞生物体中的UPR信号。线虫需要IRE-L介导的XBP-1mRNA剪接来实现UPR基因的转录和在ER胁迫下的生存。此外，IRE-1/XBP-1与Pek-1(一种介导翻译衰减的蛋白激酶)在对蠕虫发育和生存至关重要的互补途径中发挥作用。我们认为，IRE-1对UPR转录的激活以及Pek-1对翻译的抑制维持了ER的动态平衡。结果表明，UPR和ER的动态平衡对于后生动物的发育是必不可少的。
The unfolded protein response (UPR) is a transcriptional and translational intracellular signaling pathway activated by the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). We have used C. elegans as a genetic model system to dissect UPR signaling in a multicellular organism. C. elegans requires ire-l-mediated splicing of xbp-1 mRNA for UPR gene transcription and survival upon ER stress. In addition, ire-1/xbp-1 acts with pek-1, a protein kinase that mediates translation attenuation, in complementary pathways that are essential for worm development and survival. We propose that UPR transcriptional activation by ire-1 as well as translational attenuation by pek-1 maintain ER homeostasis. The results demonstrate that the UPR and ER homeostasis are essential for metazoan development.