Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, Japan.
Biosci Biotechnol Biochem. 2022 May 24;86(6):739-746. doi: 10.1093/bbb/zbac038.
Upon endoplasmic reticulum (ER) stress, eukaryotic cells commonly induce unfolded protein response (UPR), which is triggered, at least partly, by the ER stress sensor Ire1. Upon ER stress, Ire1 is dimerized or forms oligomeric clusters, resulting in the activation of Ire1 as an endoribonuclease. In ER-stressed Saccharomyces cerevisiae cells, HAC1 mRNA is spliced by Ire1 and then translated into a transcription factor that promotes the UPR. Herein, we report that Ire1 tagged artificially with irrelevant peptides at the C terminus is almost completely inactive when only dimerized, while it induced the UPR as well as untagged Ire1 when clustered. This finding suggests a fundamental difference between the dimeric and clustered forms of Ire1. By comparing UPR levels in S. cerevisiae cells carrying artificially peptide-tagged Ire1 to that in cells carrying untagged Ire1, we estimated the self-association status of Ire1 under various ER stress conditions.
当内质网（ER）受到压力时，真核细胞通常会诱导未折叠蛋白反应（UPR），该反应至少部分是由 ER 应激传感器 Ire1 触发的。在内质网受到压力时，Ire1 二聚化或形成寡聚体簇，从而激活作为内切核酸酶的 Ire1。在 ER 受到压力的酿酒酵母细胞中，HAC1 mRNA 被 Ire1 剪接，然后翻译成一种转录因子，促进 UPR。在此，我们报告说，当仅二聚化时，C 末端带有不相关肽的人工标记的 Ire1 几乎完全失活，而当聚集时，它会诱导 UPR 以及未标记的 Ire1。这一发现表明 Ire1 的二聚体和聚集形式之间存在根本差异。通过比较携带人工肽标记的 Ire1 的酿酒酵母细胞和携带未标记的 Ire1 的细胞中的 UPR 水平，我们估计了 Ire1 在各种 ER 应激条件下的自组装状态。
