内质应力传感器Ire1和PERK的应力感知和调控机制

IF 0.7
Yuki Ishiwata‐Kimata, G. Q. Le, Y. Kimata
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引用次数: 3

摘要

Ire1及其家族蛋白PERK是内质网(ER)应激传感器,可启动细胞对内质网未折叠蛋白积累的反应。正如本文所回顾的,许多出版物描述了酵母Ire1感知ER条件并受到调节的分子机制。我们还介绍了最近的研究表明,哺乳动物Ire1 (Ire1 α)和PERK以类似但不完全相同的方式控制。内质网定位分子伴侣BiP捕获这些内质网应激传感器并抑制其活性。有趣的是,Ire1不是作为伴侣底物与BiP结合,而是作为一种独特的配体。内质网中积累的未折叠蛋白促进Ire1-BiP复合物的解离。此外,Ire1直接与未折叠的蛋白质结合,导致其簇形成和有效激活。PERK也捕获未折叠的蛋白质,然后形成自寡聚物。同时,膜脂异常可能独立于未折叠蛋白的内质网积累而激活这些内质网应激传感器。此外,还有一些报告涉及控制这些内质网应激传感器活动的其他因素。这些内质网应激传感器的多种调节机制可能有助于其活动的微调。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stress-sensing and regulatory mechanism of the endoplasmic-stress sensors Ire1 and PERK
Abstract Ire1 and its family protein PERK are endoplasmic reticulum (ER)-stress sensors that initiate cellular responses against ER accumulation of unfolded proteins. As reviewed in this article, many publications describe molecular mechanisms by which yeast Ire1 senses ER conditions and gets regulated. We also cover recent studies which reveal that mammalian Ire1 (IRE1α) and PERK are controlled in a similar but not exactly the same manner. ER-located molecular chaperone BiP captures these ER-stress sensors and suppresses their activity. Intriguingly, Ire1 is associated with BiP not as a chaperone substrate, but as a unique ligand. Unfolded proteins accumulated in the ER promote dissociation of the Ire1-BiP complex. Moreover, Ire1 is directly bound with unfolded proteins, leading to its cluster formation and potent activation. PERK also captures unfolded proteins and then forms self-oligomers. Meanwhile, membrane-lipid aberrancy is likely to activate these ER-stress sensors independently of ER accumulation of unfolded proteins. In addition, there exist a number of reports that touch on other factors that control activity of these ER-stress sensors. Such a multiplicity of regulatory mechanisms for these ER-stress sensors is likely to contribute to fine tuning of their activity.
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