XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
复制标题
DOI：
10.1016/s0092-8674(01)00611-0
复制
发表时间：
2001-12-28
期刊：
影响因子：
64.5
通讯作者：
Mori, K
中科院分区：
文献类型：
--
作者：
Yoshida, H;Matsui, T;Mori, K
在酵母中，内质网应激激活的跨膜蛋白激酶/核糖核酸内切酶Ire 1 p切割HAC 1 mRNA，导致产生激活未折叠蛋白反应（UPR）的转录因子Hac 1 p。在哺乳动物中，尽管Ire 1 p同源物存在于内质网中，但尚未发现Hac 1 p对应物。相反，对哺乳动物UPR特异性的转录因子ATF 6受膜内蛋白水解调节。在这里，我们确定了转录因子XBP 1，一个目标的ATF 6，作为哺乳动物的基板，这种非常规的mRNA剪接系统，并表明，只有剪接形式的XBP 1可以有效地激活UPR。我们的研究结果揭示了在进化过程中保守的UPR特征，并阐明了IRE 1和ATF 6依赖性通路之间的关系。
In yeast, the transmembrane protein kinase/endoribonuclease Ire1p activated by endoplasmic reticulum stress cleaves HAC1 mRNA, leading to production of the transcription factor Hac1p that activates the unfolded protein response (UPR). In mammals, no Hac1p counterpart has yet been discovered despite the presence of Ire1p homologs in the endoplasmic reticulum. Instead, the transcription factor ATF6 specific to the mammalian UPR is regulated by intramembrane proteolysis. Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. Our results reveal features of the UPR conserved during evolution and clarify the relationship between IRE1- and ATF6-dependent pathways.