REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR GENE-EXPRESSION BY SP1 - PHYSICAL AND FUNCTIONAL INTERACTIONS OF SP1 AT GC BOXES AND AT A CT ELEMENT
REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR GENE-EXPRESSION BY SP1 - PHYSICAL AND FUNCTIONAL INTERACTIONS OF SP1 AT GC BOXES AND AT A CT ELEMENT
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DOI：
10.1210/me.9.9.1147
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发表时间：
1995-09-01
影响因子：
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通讯作者：
LEROITH, D
中科院分区：
文献类型：
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作者：
BEITNERJOHNSON, D;WERNER, H;LEROITH, D
胰岛素样生长因子I（IGF-I）受体介导IGF的信号转导，在生长发育中发挥关键作用。大鼠IGF-I受体基因的近端启动子区包含多个Sp1共有结合位点（GC盒），将与荧光素酶报告基因融合的各种启动子片段与Sp1表达载体一起瞬时共转染到缺乏内源Sp1的果蝇Schneider细胞中。含有 476 个核苷酸的 5'-侧翼区和 640 个核苷酸的 5'-非翻译区的近端启动子片段被 Spl 强烈激活（平均 116 倍），并且顺序删除 GC 盒的启动子的渐进性 5'-删除使 Sp1 激活降低至基础启动子活性的 15 倍，使用纯化的 Sp1 蛋白的 DNase I 足迹研究揭示了在启动子的 5'-侧翼区域以及结合 Sp1 的 5'-非翻译区中的一个同型嘌呤/同型嘧啶基序（CT 元件）。 CT元件的突变使Spl激活降低了70%。总之，这些结果证明Spl可以通过作用于启动子5'-侧翼区的GC盒和5'-非翻译区的CT元件来调节IGF-I受体启动子的表达。
The insulin-like growth factor I (IGF-I) receptor mediates signal transduction by the IGFs and plays a critical role in growth and development, The proximal promoter region of the rat IGF-I receptor gene contains multiple Sp1 consensus-binding sites (GC boxes), Various promoter fragments fused to a luciferase reporter gene were transiently cotransfected together with an Sp1 expression vector into Drosophila Schneider cells, which lack endogenous Sp1. A proximal promoter fragment containing 476 nucleotides of 5'-flanking region and 640 nucleotides of 5'-untranslated region was strongly activated by Spl (an average of 116-fold), and progressive 5'-deletions of the promoter that sequentially removed GC boxes reduced Sp1 activation to 15-fold over basal promoter activity, DNase I footprinting studies with purified Sp1 protein revealed four GC boxes in the 5'-flanking region of the promoter and one homopurine/homopyrimidine motif (CT element) in the 5'-untranslated region that bound Sp1. Mutation of the CT element reduced Spl activation by 70%, Taken together, these results demonstrate that Spl can regulate expression of the IGF-I receptor promoter by acting both on GC boxes in the 5'-flanking region of the promoter and on a CT element in the 5'-untranslated region.