Molander C, Hackzell A, Ohta M, Izumi H, Funa K
Institute of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden.
Mol Biol Rep. 2001;28(4):223-33. doi: 10.1023/a:1015701232589.
The mouse PDGF beta-receptor promoter is tightly controlled by NF-Y that binds to a CCAAT box located upstream of the initiation site [1, 2]. In this report, we show that Sp1 plays an essential role in the PDGF beta-receptor transcription. Within the upstream GC rich area there are two Sp1 binding sites located in close proximity to the CCAAT box. Deletion of the GC rich region resulted in a 50% decrease of the transcriptional activity of the promoter, and a complete loss of its responsiveness to over-expression of Sp1. There was an additive effect between NF-Y and Sp I in reporter activity when they were co-transfected together with the promoter-reporter construct. Furthermore, transfection of NF-Y failed to enhance transcriptional activity when the Sp1 binding sites were deleted from the promoter, suggesting an important role for Sp1 in this NF-Y controlled transcription. We have recently reported that c-Myc represses PDGF beta-receptor transcription through its interference with the transactivation activity of NF-Y [3]. In the case of p21(wafl/cip1) transcription, c-Myc was shown to repress its transcription by sequestering Sp1 [4]. However, we could not find any effect of Sp1 in the c-Myc-mediated repression on the PFDGF beta-receptor promoter, since the deletion of SpI binding sites could not attenuate the repression by c-Myc on the promoter activity.
小鼠血小板衍生生长因子β受体启动子受NF-Y严格调控，NF-Y与起始位点上游的一个CCAAT盒结合[1,2]。在本报告中，我们表明Sp1在血小板衍生生长因子β受体转录中起关键作用。在上游富含GC的区域内，有两个Sp1结合位点紧邻CCAAT盒。富含GC区域的缺失导致启动子转录活性降低50%，并且完全丧失了对Sp1过表达的反应性。当NF-Y和Sp1与启动子-报告基因构建体共转染时，它们在报告基因活性方面具有累加效应。此外，当从启动子中删除Sp1结合位点时，NF-Y的转染未能增强转录活性，这表明Sp1在这种由NF-Y控制的转录中起重要作用。我们最近报道，c-Myc通过干扰NF-Y的反式激活活性来抑制血小板衍生生长因子β受体转录[3]。在p21(wafl/cip1)转录的情况下，c-Myc被证明通过隔离Sp1来抑制其转录[4]。然而，我们未发现Sp1在c-Myc介导的对血小板衍生生长因子β受体启动子的抑制中有任何作用，因为删除Sp1结合位点并不能减弱c-Myc对启动子活性的抑制。
