IRE1 and efferent signaling from the endoplasmic reticulum.
IRE1 and efferent signaling from the endoplasmic reticulum.
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DOI：
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发表时间：
2000-11
影响因子：
4
通讯作者：
F. Urano;A. Bertolotti;D. Ron
中科院分区：
文献类型：
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作者：
F. Urano;A. Bertolotti;D. Ron
对细胞对内质网错误折叠蛋白的适应(未折叠蛋白反应-UPR)的遗传分析揭示了一种新的信号通路，该信号通路是由内质网驻留的蛋白激酶和内切酶IRE1激活启动的。在酵母中，Ire1p通过促进非常规剪接事件激活基因表达，该剪接事件将编码Hac1p转录因子的mRNA从低效翻译的非活性mRNA转换为主动翻译的mRNA。Hac1p结合编码伴侣基因的启动子和UPR的其他靶标并激活它们。最近，哺乳动物的IRE1同源物已被发现，它们对内质网应激的反应是通过与内质网伴侣蛋白Bip结合来调节的。哺乳动物的IRE1激活基因表达的机制尚未完全确定，哺乳动物的HAC1同源物也尚未确定。令人惊讶的是，哺乳动物的IRE1能够激活Jun N末端激酶和转录因子ATF6介导的另一种内质网应激信号通路。这表明哺乳动物的UPR比在酵母中发现的更加复杂。
Genetic analysis of the cellular adaptation to malfolded proteins in the endoplasmic reticulum (the unfolded protein response - UPR) has revealed a novel signaling pathway initiated by activation of IRE1, an ER-resident protein kinase and endonuclease. In yeast, Ire1p activates gene expression by promoting a non-conventional splicing event that converts the mRNA encoding the Hac1p transcription factor from an inefficiently translated inactive mRNA to an actively translated one. Hac1p binds to the promoters of genes encoding chaperones and other targets of the UPR and activates them. Recently, mammalian IRE1 homologues have been identified and their response to ER stress is regulated by binding to the ER chaperone BiP. The mechanisms by which mammalian IRE1 activates gene expression have not been completely characterized and mammalian HAC1 homologues have not been identified. Surprisingly, mammalian IRE1s are able to activate both JUN N-terminal kinases and an alternative ER-stress signaling pathway mediated by the transcription factor ATF6. This indicates that the mammalian UPR is more complex than that found in yeast.