CREB and Sp1 regulate the human MAP gene promoter activity in renal tubular epithelial cells
CREB and Sp1 regulate the human MAP gene promoter activity in renal tubular epithelial cells
复制标题
CREB 和 Sp1 调节肾小管上皮细胞中人 CD2AP 基因启动子活性。
DOI：
10.1016/j.abb.2008.03.031
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发表时间：
2008-06-01
影响因子：
3.9
通讯作者：
Zhou, Guo-Ping
中科院分区：
文献类型：
--
作者：
Lu, Chao;Ren, Wei;Zhou, Guo-Ping
人CD2相关蛋白(CD2AP)参与多种分子信号通路，是肾病综合征的重要致病因子。在此，我们鉴定了人CD2AP基因在肾小管上皮细胞中的转录起始点和启动子区域。通过荧光素酶活性检测和缺失分析，我们发现在转录起始点之前的-558和-1bp之间的区域对于人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CD2AP启动子的基本转录活性是必不可少的。过表达磷酸化的CREB和Sp1可反式激活人CD2AP启动子，而小干扰RNA介导的阻断CREB和Sp1基因表达则显著抑制其活性。这些发现首次对人CD2AP基因启动子进行了分析，表明不仅CREB而且Sp1在调节肾小管上皮细胞CD2AP启动子的基础活性方面起着关键作用。(C)2008 Elsevier Inc.保留所有权利。
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.