Divergence and Conservation of the Major UPR Branch IRE1-bZIP Signaling Pathway across Eukaryotes.
Divergence and Conservation of the Major UPR Branch IRE1-bZIP Signaling Pathway across Eukaryotes.
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DOI：
10.1038/srep27362
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发表时间：
2016-06-03
影响因子：
4.6
通讯作者：
Wang A
中科院分区：
文献类型：
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作者：
Zhang L;Zhang C;Wang A
未折叠蛋白反应（UPR）通过调节细胞对内质网（ER）中非生物和生物信号（如热休克和病毒感染）施加的应激反应，对生命至关重要。由IRE1介导的酵母HAC1、植物bZIP60和后生动物XBP1的非常规剪接激活的肌醇要求酶1 （insitol requiring enzyme 1, IRE1）信号通路是UPR最古老的分支。在这项研究中，我们系统地检测了酵母IRE1p-HAC1、植物IRE1A/IRE1B-bZIP60和人类hIRE1-XBP1对。我们发现，与bZIP60不同，XBP1不能在酵母中交换HAC1p，并且HAC1p、bZIP60和XBP1之间不允许发生种间异型相互作用。这些数据证明了IRE1-bZIP下游信号的进化分化。我们还发现植物IRE1s的双胞质结构域在体内的作用机制与IRE1p和hIRE1一致，并且植物IRE1B不仅与IRE1p相互作用，而且在酵母中形成典型的IRE1动态灶。因此，IRE1信号分支的上游组成部分，包括IRE1激活和作用机制是高度保守的。综上所述，这些数据促进了对跨王国IRE1信号通路进化分化和保护的分子理解。
The unfolded protein response (UPR) is crucial to life by regulating the cellular response to the stress in the endoplasmic reticulum (ER) imposed by abiotic and biotic cues such as heat shock and viral infection. The inositol requiring enzyme 1 (IRE1) signaling pathway activated by the IRE1-mediated unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans, is the most ancient branch of the UPR. In this study, we systematically examined yeast IRE1p-HAC1, plant IRE1A/IRE1B-bZIP60 and human hIRE1-XBP1 pairs. We found that, unlike bZIP60, XBP1 is unable to functionally swap HAC1p in yeast, and that the inter-species heterotypic interactions among HAC1p, bZIP60 and XBP1 are not permitted. These data demonstrate evolutionary divergence of the downstream signaling of IRE1-bZIP. We also discovered that the dual cytosolic domains of plant IRE1s act in vivo in a mechanism consistent with IRE1p and hIRE1, and that plant IRE1B not only interacts with IRE1p but also forms typical IRE1 dynamic foci in yeast. Thus, the upstream components of the IRE1 signaling branch including IRE1 activation and action mechanisms are highly conserved. Taken together these data advance the molecular understanding of evolutionary divergence and conservation of the IRE1 signaling pathway across kingdoms.