IDX-1 - A NEW HOMEODOMAIN TRANSCRIPTION FACTOR EXPRESSED IN RAT PANCREATIC-ISLETS AND DUODENUM THAT TRANSACTIVATES THE SOMATOSTATIN GENE
IDX-1 - A NEW HOMEODOMAIN TRANSCRIPTION FACTOR EXPRESSED IN RAT PANCREATIC-ISLETS AND DUODENUM THAT TRANSACTIVATES THE SOMATOSTATIN GENE
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DOI：
10.1002/j.1460-2075.1994.tb06363.x
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发表时间：
1994-03-01
期刊：
影响因子：
11.4
通讯作者：
HABENER, JF
中科院分区：
文献类型：
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作者：
MILLER, CP;MCGEHEE, RE;HABENER, JF
我们从大鼠胰岛生长抑素产生细胞系克隆了一种新的同源蛋白IDX-1(胰岛/十二指肠同源盒-1)，该基因与果蝇黑腹同源盒蛋白Antennapedia(ANTP)和非洲爪哇内胚层特异性同源蛋白X1Hbox8序列非常相似。对大鼠组织中IDX-1mRNA和蛋白的分析表明，IDX-1在胰岛、胰管和十二指肠均有表达。在凝胶迁移率改变分析中，ZDX-1与大鼠生长抑素基因5‘侧翼区的三个位点结合。在共转染实验中，IDX-1反式激活含有生长抑素启动子序列的报告构建体，而IDX-1结合位点的突变会减弱反式激活。利用编码同源蛋白的mRNAs的简并扩增对胰岛RNA进行逆转录聚合酶链式反应，结果表明IDX-1是在成年大鼠胰岛表达的12种不同的ANTP样同源结构域mRNAs中含量最高的。IDX-1的表达模式、相对丰度和转录调节活性表明，IDX-1可能参与内分泌胰腺和十二指肠的胰岛激素基因的调节和细胞分化。
We describe the cloning from a rat islet somatostatin-producing cell line of a 1.4 kb cDNA encoding a new homeoprotein, IDX-1 (islet/duodenum homeobox-1), with close sequence similarity to the Drosophila melanogaster homeobox protein Antennapedia (Antp) and the Xenopus laevis endoderm-specific homeoprotein XlHbox8. Analyses of IDX-1 mRNA and protein in rat tissues show that IDX-1 is expressed in pancreatic islets and ducts and in the duodenum. In electrophoretic mobility shift assays ZDX-1 binds to three sites in the 5' flanking region of the rat somatostatin gene. In co-transfection experiments IDX-1 transactivates reporter constructs containing somatostatin promoter sequences, and mutation of the IDX-1 binding sites attenuates transactivation. Reverse transcription- polymerase chain reaction of islet RNA using degenerate amplimers for mRNAs encoding homeoproteins indicates that IDX-1 is the most abundant of 12 different Antp-like homeodomain mRNAs expressed in adult rat islets. The pattern of expression, relative abundance and transcriptional regulatory activity suggests that IDX-1 may be involved in the regulation of islet hormone genes and in cellular differentiation in the endocrine pancreas and the duodenum.