Yap Wei Sheng, Thibault Guillaume
School of Biological Sciences, Nanyang Technological University, Singapore, 637551.
Mechanobiology Institute, National University of Singapore, Singapore, 117411.
MicroPubl Biol. 2022 Jun 28;2022. doi: 10.17912/micropub.biology.000592. eCollection 2022.
Protein folding and quality control is tightly regulated at the endoplasmic reticulum (ER), and its disruption is associated with many diseases. In eukaryotes, the accumulation of unfolded protein in the ER is sensed by the three sensors, IRE1, PERK, and ATF6 to activate the unfolded protein response (UPR) to restore ER homeostasis. However, uncoupling the sensing of each sensor and their respective downstream pathways has been challenging as the absence of one is compensated by the remaining two sensors. Here, we report a fully functional human PERK (hPERK) chimeric protein expressed in that could be used for high throughput screen to identify new PERK inhibitory or activating compounds as well as to characterize the PERK stress sensing mechanisms.
蛋白质折叠和质量控制在内质网（ER）中受到严格调控，其破坏与许多疾病相关。在真核生物中，内质网中未折叠蛋白的积累由三种传感器IRE1、PERK和ATF6感知，以激活未折叠蛋白反应（UPR）来恢复内质网稳态。然而，由于缺失一种传感器会被其余两种传感器补偿，因此将每个传感器的感知与其各自的下游途径解耦一直具有挑战性。在这里，我们报告了一种在[具体表达系统]中表达的功能齐全的人PERK（hPERK）嵌合蛋白，该蛋白可用于高通量筛选，以鉴定新的PERK抑制或激活化合物，以及表征PERK应激感应机制。
