非折叠蛋白反应——一条综合的细胞内信号通路

An Integrated Intracellular Signaling Pathway-UPR

内质网(endoplasmic reticulum,ER)作为细胞中蛋白成熟的场所,可以很敏感的感受细胞内外环境的变化。当ER内环境改变,细胞就会激活信号应对这些改变,并且重新恢复折叠蛋白的环境。内质网的这种改变就是内质网应激(endoplasmic reticulum stress,ERS),而对这种应激作出的反应就是非折叠蛋白反应[1(]Unfolded Protein Response,UPR)。UPR至少引起了3种不同的信号通路,这些通路不仅调控分泌途径中大部分基因的表达,而且还广泛影响细胞的各个方面包括蛋白质、氨基酸和脂类的代谢。同时,这3条通路可以综合的调控细胞分泌器官的重塑并根据ERS重新调节细胞的生理活性。就UPR相关的感受器及其信号通路作简要的介绍。

In cells,the ER functions as the organelle where proteins mature,and as such,is very responsive to extracellular-intracellular changes of environment. When ER luminal conditions are altered,the cell activates signaling cascades that attempt to deal with the altered conditions and restore a favorable folding environment. Such alterations are referred to as ER stress,and the response activated is the unfolded protein response （UPR）, Together,at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids, The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress.