Xu Rang, Zhang Ping, Huang Jian, Ge ShengFang, Lu Jian, Qian GuanXiang
Research Center for Human Gene Therapy, Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Biochem Biophys Res Commun. 2007 Apr 27;356(1):286-92. doi: 10.1016/j.bbrc.2007.02.140. Epub 2007 Mar 5.
Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. In this study, we cloned and identified the proximal 269 bp promoter of survivin gene, which exhibited strong promoter activity in HeLa cells. The TATA-less, GC-rich promoter contains 7 putative binding sites for Sp1, two of which (one at position -148 to -153, the other at position -127 to -140) are essential in regulating basal survivin promoter activity. Not only Sp1 but also Sp3 can activate the survivin promoter, which were proven by EMSA, blocking Sp1 or Sp3 using RNAi or mithramycin treatment of HeLa cells, and overexpression of Sp1 or Sp3. Our results collectively suggest that Sp1 cooperates with Sp3 to regulate survivin promoter activity.
生存素是凋亡抑制蛋白家族的一个独特成员，在许多癌症中过度表达，并被认为在肿瘤发生中起重要作用。在本研究中，我们克隆并鉴定了生存素基因近端269 bp的启动子，其在HeLa细胞中表现出强大的启动子活性。该无TATA盒、富含GC的启动子包含7个假定的Sp1结合位点，其中两个位点（一个位于-148至-153位，另一个位于-127至-140位）在调节生存素启动子的基础活性中至关重要。不仅Sp1，而且Sp3都可以激活生存素启动子，这通过电泳迁移率变动分析（EMSA）、使用RNA干扰或光神霉素处理HeLa细胞来阻断Sp1或Sp3以及Sp1或Sp3的过表达得到证实。我们的结果共同表明，Sp1与Sp3协同调节生存素启动子活性。
