未折叠蛋白质应答

Advance in study of unfolded protein response

内质网是真核细胞中蛋白质合成、折叠与分泌的重要细胞器。细胞进化出一套完整的机制来监督和帮助内质网内蛋白质的折叠与修饰。而当错误折叠的蛋白质累积时,细胞通过一系列信号转导途径,对其进行应答,包括增强蛋白质折叠能力、停滞大多数蛋白质的翻译、加速蛋白质的降解等。如果内质网功能紊乱持续,细胞将最终启动凋亡程序。这些反应被统称为未折叠蛋白质应答(unfolded protein response,UPR)。UPR是多个信号转导通路的总称,包括IRE1-XBP1、PERK-ATF4以及ATF6等信号途径。除了应激条件外,UPR还被用于正常生理条件下的调节,例如胆固醇合成代谢的负反馈调控。

The endoplasmic reticulum （ER） is an organelle for membrane and secretary proteins synthesis, folding and export. Cells develop a quality control system to make sure that only correctly folded proteins exit from the ER. Once unfolded proteins accumulate in ER, a signal transduction will be triggered to start a series of processes called unfolded protein response （UPR）, including protein folding accelerating, translation attenuation, ER-associated degradation and so on. IRE1-XBP1, PERK-ATF4 and ATF6 are three main signal pathways in UPR. Besides stress conditions, UPR also plays roles in physiological conditions, such as feedback control of cholesterol synthesis.