School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Jan;1865(1):158449. doi: 10.1016/j.bbalip.2019.04.009. Epub 2019 Apr 24.
The unfolded protein response (UPR) is activated by endoplasmic reticulum (ER) stress and is designed to restore cellular homeostasis through multiple intracellular signalling pathways. In mammals, the UPR programme regulates the expression of hundreds of genes in response to signalling from ATF6, IRE1, and PERK. These three highly conserved stress sensors are activated by the accumulation of unfolded proteins within the ER. Alternatively, IRE1 and PERK sense generalised lipid bilayer stress (LBS) at the ER while ATF6 is activated by an increase of specific sphingolipids. As a result, the UPR supports cellular robustness as a broad-spectrum compensatory pathway that is achieved by deploying a tailored transcriptional programme adapted to the source of ER stress. This review summarises the current understanding of the three ER stress transducers in sensing proteotoxic stress and LBS. The plasticity of the UPR programme in the context of different sources of ER stress will also be discussed.
未折叠蛋白反应（UPR）是由内质网（ER）应激激活的，旨在通过多种细胞内信号通路恢复细胞内稳态。在哺乳动物中，UPR 程序通过来自 ATF6、IRE1 和 PERK 的信号调节数百个基因的表达。这三个高度保守的应激传感器通过 ER 内未折叠蛋白的积累而被激活。或者，IRE1 和 PERK 感知 ER 中的广义脂双层应激（LBS），而 ATF6 则通过特定鞘脂的增加而被激活。因此，UPR 作为一种广谱补偿途径支持细胞稳健性，该途径通过部署适应 ER 应激源的定制转录程序来实现。这篇综述总结了目前对内质网应激传感器在感知蛋白毒性应激和 LBS 方面的理解。还将讨论 UPR 程序在不同 ER 应激源情况下的可塑性。
