Gupta Ananya, Read Danielle E, Gupta Sanjeev
Discipline of Pathology, School of Medicine, National University of Ireland, Galway, Ireland.
Methods Mol Biol. 2015;1292:19-38. doi: 10.1007/978-1-4939-2522-3_2.
The endoplasmic reticulum (ER) is responsible for the proper folding and processing of secreted and transmembrane proteins within the cell. Stimuli that disrupt ER function cause an accumulation of misfolded proteins within the ER lumen, a condition termed ER stress. The unfolded protein response (UPR) is activated in response to ER stress in an attempt to restore ER homeostasis. UPR is initiated by three transmembrane sensors that activate three signaling pathways which lead to the activation of transcription factors and production of chaperones. The coordinated action of these three pathways attempt to restore homeostasis. However, if the ER homeostasis cannot be restored, it initiates apoptosis. Deregulated or compromised functions of these pathways can therefore lead to the pathogenesis of disease. In order to understand the molecular mechanisms involved, it is important to study each pathway independently. Here, we describe a number of approaches to selectively target each arm of UPR and investigate the functional significance of the UPR pathway involved.
内质网（ER）负责细胞内分泌蛋白和跨膜蛋白的正确折叠与加工。破坏内质网功能的刺激会导致内质网腔中错误折叠蛋白的积累，这种情况称为内质网应激。未折叠蛋白反应（UPR）会在内质网应激时被激活，试图恢复内质网的稳态。UPR由三种跨膜传感器启动，它们激活三条信号通路，进而导致转录因子的激活和伴侣蛋白的产生。这三条通路的协同作用试图恢复稳态。然而，如果内质网稳态无法恢复，就会引发细胞凋亡。因此，这些通路的失调或功能受损会导致疾病的发病机制。为了理解其中涉及的分子机制，独立研究每条通路很重要。在此，我们描述了一些选择性靶向UPR各分支的方法，并研究了相关UPR通路的功能意义。
