The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters.
The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters.
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DOI：
10.1016/s0021-9258(18)45916-9
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发表时间：
1992-02
期刊：
影响因子：
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通讯作者：
Daniel P. McCauliffeS;Yih-Sheng Yang;Jeff Wilson;Richard D. Sontheimert;J. D. Capral
中科院分区：
文献类型：
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作者：
Daniel P. McCauliffeS;Yih-Sheng Yang;Jeff Wilson;Richard D. Sontheimert;J. D. Capral
钙网蛋白（CR）是一种钙结合蛋白，存在于内质网和肌浆网中，与人Ro/SS-A自身免疫血清反应。我们使用人类CR cDNA分离了一个6千碱基的人类基因组克隆，该克隆包含529个碱基对，9个外显子，8个内含子，以及数百个碱基对3'的聚腺苷酸化序列。对人类CR启动子区域的分析显示，在人类GRP78、GRP94和蛋白质二硫异构酶启动子中也发现了许多潜在的调控位点，包括多个Sp1和CCAAT共识序列、一个AP-2识别序列（蛋白质二硫异构酶中不存在）和多个富含gc的区域。DNA足迹和凝胶位移分析表明，cr5 '-侧翼区域与人类核提取物中发现的蛋白质结合，而不是小鼠核提取物。该序列与先前确定的人类GRP78和GRP94启动子的调控序列同源。这些数据表明，CR、GRP78、GRP94和蛋白二硫异构酶可能在一定程度上具有相似的转录调控，表明它们的基因产物虽然结构不同，但可能具有相似的功能或协同功能。这些观察结果是额外的兴趣，因为所有这四个基因编码的酸性蛋白定位于内质网。
Calreticulin (CR) is a calcium binding protein that resides in the endoplasmic and sarcoplasmic reticulum and is reactive with human Ro/SS-A autoimmune sera. We have used human CR cDNA to isolate a human 6-kilobase genomic clone that contains 529 base pairs upstream of the presumed transcription start site, 9 exons, 8 introns, and several hundred base pairs 3' of a polyadenylation sequence. Analysis of the human CR promoter region reveals a number of potential regulatory sites also found in the human GRP78, GRP94, and protein disulfide isomerase promoters, including multiple Sp1 and CCAAT consensus sequences, an AP-2 recognition sequence (absent in protein disulfide isomerase), and multiple GC-rich areas. DNA footprint and gel shift analysis on the CR 5'-flanking region demonstrates an area that is bound by protein found in human but not murine nuclear extracts. This sequence is homologous with previously determined regulatory sequences of the human GRP78 and GRP94 promoters. These data indicate that CR, GRP78, GRP94, and protein disulfide isomerase may in part have similar transcriptional regulation and suggest that their gene products while structurally distinct may have similar functions or co-functions. These observations are of additional interest as all four of these genes encode acidic proteins that localize to the endoplasmic reticulum.