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CREB and Sp1 regulate the human MAP gene promoter activity in renal tubular epithelial cells

机译:CREB和Sp1调节肾小管上皮细胞中人MAP基因启动子的活性

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摘要

The human CD2-associated protein (CD2AP) is involved in several molecular signaling pathways and is an important factor responsible for nephrotic syndrome. Here we report the identification of the transcription start point and promoter region of the human CD2AP gene in renal tubular epithelial cells. With luciferase assays and deletion analysis, we found that the region between -558 and -1 bp ahead of the transcription start point is indispensable for the promoter activity of the human CD2AP gene. A CREB site and two Sp1 sites were essential for maintaining the basal transcriptional activity of the human CD2AP promoter. Overexpression of phosphorylated CREB and Sp1 transactivated the human CD2AP promoter, whereas small interfering RNA-mediated blockage of CREB and Sp1 genes expressions inhibited markedly its activity. These findings provide the first analysis of the human CD2AP gene promoter and demonstrate that not only CREB but also Sp1 plays a critical role in regulating basal CD2AP promoter activity in renal tubular epithelial cells. (C) 2008 Elsevier Inc. All rights reserved.
机译:人CD2相关蛋白(CD2AP)参与多种分子信号通路,并且是导致肾病综合征的重要因素。在这里,我们报告在肾小管上皮细胞中人类CD2AP基因的转录起点和启动子区域的鉴定。通过萤光素酶测定和缺失分析,我们发现转录起点之前-558至-1 bp之间的区域对于人类CD2AP基因的启动子活性是必不可少的。一个CREB位点和两个Sp1位点对于维持人类CD2AP启动子的基础转录活性至关重要。磷酸化的CREB和Sp1的过表达激活了人类CD2AP启动子,而小的干扰RNA介导的CREB和Sp1基因表达的阻断显着抑制了其活性。这些发现提供了对人类CD2AP基因启动子的首次分析,并证明了不仅CREB,而且Sp1在调节肾小管上皮细胞的基础CD2AP启动子活性中也起着关键作用。 (C)2008 Elsevier Inc.保留所有权利。

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