Schröder Martin, Kaufman Randal J
School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, United Kingdom.
Annu Rev Biochem. 2005;74:739-89. doi: 10.1146/annurev.biochem.73.011303.074134.
In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure. When protein folding in the ER is inhibited, signal transduction pathways, which increase the biosynthetic capacity and decrease the biosynthetic burden of the ER to maintain the homeostasis of this organelle, are activated. These pathways are called the unfolded protein response (UPR). In this review, we briefly summarize principles of protein folding and molecular chaperone function important for a mechanistic understanding of UPR-signaling events. We then discuss mechanisms of signal transduction employed by the UPR in mammals and our current understanding of the remodeling of cellular processes by the UPR. Finally, we summarize data that demonstrate that UPR signaling feeds into decision making in other processes previously thought to be unrelated to ER function, e.g., eukaryotic starvation responses and differentiation programs.
在内质网（ER）中，分泌蛋白和跨膜蛋白折叠成其天然构象，并经历对其活性和结构至关重要的翻译后修饰。当内质网中的蛋白质折叠受到抑制时，信号转导通路会被激活，这些通路会增加内质网的生物合成能力并减轻其生物合成负担，以维持该细胞器的稳态。这些通路被称为未折叠蛋白反应（UPR）。在这篇综述中，我们简要总结了蛋白质折叠的原理和分子伴侣功能，这对于从机制上理解UPR信号事件很重要。然后，我们讨论了哺乳动物中UPR所采用的信号转导机制以及我们目前对UPR对细胞过程重塑的理解。最后，我们总结了一些数据，这些数据表明UPR信号参与了先前认为与内质网功能无关的其他过程中的决策，例如真核生物的饥饿反应和分化程序。
