The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex
The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex
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DOI：
10.1093/nar/27.6.1437
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发表时间：
1999-03-15
影响因子：
14.9
通讯作者：
Lee, AS
中科院分区：
文献类型：
--
作者：
Roy, B;Lee, AS
当哺乳动物细胞遭受钙耗竭应激或蛋白质糖基化阻断时，编码内质网（ER）伴侣蛋白的葡萄糖调节蛋白（GRP）基因家族的转录会被诱导至高水平。在grp启动子中保守的哺乳动物内质网应激反应元件（ERSE）由一个三联体结构CCAAT（N - 9）CCACG组成，其中N是一个9bp的富含CC的区域。两个重复的ERSE能够以序列特异性但方向无关的方式赋予异源启动子完全的应激诱导性。除了CBF/NF - Y和YY1分别与CCAAT和CCACG基序结合外，我们还进一步发现，来自HeLa细胞核提取物的内质网应激诱导复合物（ERSF）特异性地与ERSE结合。引人注目的是，ERSF与ERSE的相互作用需要9bp区域内一个保守的GGC基序。由于GGC三联体序列的突变也会导致应激诱导性的丧失，所以9bp区域内的特定序列是三联体结构的一个组成部分。最后，因子结合与应激诱导性的相关性表明：ERSF单独与ERSE结合是不够的；完全的应激诱导性需要CCAAT、GGC和CCACG序列基序的完整性，以及这些位点之间精确的间距。
When mammalian cells are subjected to calcium depletion stress or protein glycosylation block, the transcription of a family of glucose-regulated protein (GRP) genes encoding endoplasmic reticulum (ER) chaperones is induced to high revels. The consensus mammalian ER stress response element (ERSE) conserved among grp promoters consists of a tripartite structure CCAAT(N-9)CCACG, with N being a strikingly CC-rich region of 9 bp, The ERSE, in duplicate copies, can confer full stress inducibility to a heterologous promoter in a sequence-specific but orientation-independent manner. In addition to CBF/NF-Y and YY1 binding to the CCAAT and CCACG motifs, respectively, we further discovered that an ER stress-inducible complex (ERSF) from HeLa nuclear extract binds specifically to the ERSE, Strikingly, the interaction of the ERSF with the ERSE requires a conserved GGC motif within the 9 bp region. Since mutation of the GGC triplet sequence also results in loss of stress inducibility, specific sequence within the 9 bp region is an integral part of the tripartite structure. Finally, correlation of factor binding with stress inducibility reveals that: ERSF binding to the ERSE alone is not sufficient; full stress inducibility requires integrity of the CCAAT, GGC and CCACG sequence motifs, as well as precise spacing among these sites.