Analysis of molecular mechanism of sensing endoplasmic reticulum stress and effect of failing in the endoplasmic reticulum stress response

内质网（ER）膜结合转录因子ATF6在内质网应激时易位到高尔基体，并被蛋白水解激活。我们证明，仅ATF6的管腔结构域就足以感应内质网应激。ATF6α敲除小鼠发育正常，但腹腔注射内质网络应激诱导试剂tunicamycin后，ATF6α敲除小鼠出现肝功能障碍和脂肪变性。我们指出，由于载脂蛋白B-100不稳定，极低密度脂蛋白的形成受到抑制，这是肝脏释放中性脂质的原因。

The endoplasmic reticulum (ER) membrane-bound transcription factor ATF6 translocates to the Golgi apparatus upon ER stress to be activated by proteolysis. We demonstrate that the luminal domain of ATF6 alone is sufficient for sensing ER stress. ATF6α knockout mice develop normally, however, ATF6α knockout mice exhibit liver dysfunction and steatosis upon intraperitoneal injection of the ER stress-inducing reagent tunicamycin. We point out suppression of very-low-density lipoprotein formation, which is responsible for release of neutral lipids from liver, due to the destabilized apolipoprotein B-100 as a cause of liver steatosis.