Signalling from endoplasmic reticulum to nucleus: Transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway
Signalling from endoplasmic reticulum to nucleus: Transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway
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DOI：
10.1046/j.1365-2443.1996.d01-274.x
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发表时间：
1996-09-01
期刊：
影响因子：
2.1
通讯作者：
Yura, T
中科院分区：
文献类型：
--
作者：
Mori, K;Kawahara, T;Yura, T
背景资料：未折叠蛋白在内质网（ER）中的积累触发了定位于ER中的分子伴侣和折叠酶的转录诱导。因此，真核细胞具有从ER到细胞核的细胞内信号传导途径，称为未折叠蛋白反应（UPR）途径。在酿酒酵母中，这种诱导是由顺式作用的未折叠蛋白反应元件（UPRE）介导的，该元件被认为是由一个或多个转录因子识别的。然后，我们使用酵母单杂交筛选克隆了ERN 4（推测与HAC 1相同）基因，其中GAL 4-ERN 4融合基因组成型激活UPR途径。ERN 4基因编码碱性亮氨酸拉链蛋白（Ern 4p），其在体外特异性结合UPRE并在体内激活转录。缺乏Ern 4p的细胞是无法诱导转录的任何五个目标基因的测试和表现出敏感性ER应力和肌醇growth.Conclusion的要求：我们得出结论，Ern 4p代表了一个主要组成部分的推定的转录因子（UPRF）负责的UPR导致ER本地化的应力蛋白的诱导。
Background: Accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the transcriptional induction of molecular chaperones and folding enzymes localized in the ER. Thus, eukaryotic cells possess an intracellular signalling pathway from the ER to the nucleus, called the unfolded protein-response (UPR) pathway. In Saccharomyces cerevisiae, such induction is mediated by the cis-acting unfolded protein-response element (UPRE) which has been thought to be recognized by one or more transcription factor(s).Results: Extensive mutational analysis revealed that UPRE contains a partial palindrome with a spacer of one nucleotide (CAGCGTG) that is essential for its function. We then cloned the ERN4 (presumably identical with HAC1) gene using yeast one-hybrid screening, in which the GAL4-ERN4 fusion gene constitutively activates the UPR pathway. The ERN4 gene encodes a basic-leucine zipper protein (Ern4p) that specifically binds to UPRE in vitro and activates transcription in vivo. Cells lacking Ern4p are unable to induce transcription of any of the five target genes tested and exhibit sensitivity to ER stress and inositol requirement for growth.Conclusion: We concluded that Ern4p represents a major component of the putative transcription factor (UPRF) responsible for the UPR leading to the induction of ER-localized stress proteins.