Intrinsic capacities of molecular sensors of the unfolded protein response to sense alternate forms of endoplasmic reticulum stress
Intrinsic capacities of molecular sensors of the unfolded protein response to sense alternate forms of endoplasmic reticulum stress
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DOI：
10.1091/mbc.e06-01-0055
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发表时间：
2006-07-01
影响因子：
3.3
通讯作者：
Niwa, Maho
中科院分区：
文献类型：
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作者：
DuRose, Jenny B.;Tam, Arvin B.;Niwa, Maho
未折叠蛋白应答(UPR)根据细胞需求调节内质网(ER)的蛋白质折叠能力。在哺乳动物细胞中，三种ER跨膜成分IRE1、PERK和ATF6启动不同的UPR信号分支。我们发现这些UPR成分对不同形式的内质网压力表现出不同的敏感性。尤其是由内质网信号释放引起的内质网应激，揭示了UPR信号分支性质的根本差异。与IRE1和PERK对内质网应激的快速反应相比，ATF6对内质网应激的反应明显延迟。这些研究首次对UPR信号分支的激活进行了并列比较，揭示了UPR应激感受器在不同形式的内质网应激中激活的内在特征。因此，它们为了解内质网应激传感器如何提供不同的反应以及如何在生理环境中实现最佳的UPR反应提供了初步的基础。
The unfolded protein response (UPR) regulates the protein-folding capacity of the endoplasmic reticulum (ER) according to cellular demand. In mammalian cells, three ER transmembrane components, IRE1, PERK, and ATF6, initiate distinct UPR signaling branches. We show that these UPR components display distinct sensitivities toward different forms of ER stress. ER stress induced by ER Call release in particular revealed fundamental differences in the properties of UPR signaling branches. Compared with the rapid response of both IRE1 and PERK to ER stress induced by thapsigargin, an ER Call ATPase inhibitor, the response of ATF6 was markedly delayed. These studies are the first side-by-side comparisons of UPR signaling branch activation and reveal intrinsic features of UPR stress sensor activation in response to alternate forms of ER stress. As such, they provide initial groundwork toward understanding how ER stress sensors can confer different responses and how optimal UPR responses are achieved in physiological settings.