Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response
Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response
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DOI：
10.1101/cshperspect.a013169
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发表时间：
2013-03-01
影响因子：
7.2
通讯作者：
Walter, Peter
中科院分区：
文献类型：
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作者：
Gardner, Brooke M.;Pincus, David;Walter, Peter
分泌蛋白和跨膜蛋白作为未折叠蛋白进入内质网（ER），并且作为运输至其靶细胞器的折叠蛋白或作为靶向降解的错误折叠蛋白离开。未折叠蛋白反应（UPR）维持ER内的蛋白质折叠稳态，确保ER的蛋白质折叠能力满足客户蛋白的负载。UPR的激活依赖于三种ER应激传感器蛋白Ire 1、PERK和ATF6。虽然激活的后果是很好的理解，这些传感器如何检测ER应力仍然不清楚。最近的证据表明，酵母Ire1直接结合未折叠的蛋白质，这诱导其寡聚化和激活。BiP从Ire1解离调节这种寡聚平衡，最终调节Ire1的敏感性和激活持续时间。电流变应力传感的机械原理是本文的重点。
Secretory and transmembrane proteins enter the endoplasmic reticulum (ER) as unfolded proteins and exit as either folded proteins in transit to their target organelles or as misfolded proteins targeted for degradation. The unfolded protein response (UPR) maintains the protein-folding homeostasis within the ER, ensuring that the protein-folding capacity of the ER meets the load of client proteins. Activation of the UPR depends on three ER stress sensor proteins, Ire1, PERK, and ATF6. Although the consequences of activation are well understood, how these sensors detect ER stress remains unclear. Recent evidence suggests that yeast Ire1 directly binds to unfolded proteins, which induces its oligomerization and activation. BiP dissociation from Ire1 regulates this oligomeric equilibrium, ultimately modulating Ire1's sensitivity and duration of activation. The mechanistic principles of ER stress sensing are the focus of this review.