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Transcriptional activation by AP-2 alpha is modulated by the oncogene DEK

机译:AP-2 alpha的转录激活受癌基因DEK调节

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摘要

Cell differentiation and development are highly regulated processes at the transcriptional level. One of the main transcription factors that regulate these processes is AP-2alpha, a cell-type specific protein required for vertebrate development and embryogenesis. AP-2alpha also regulates apoptosis and cell-cycle specific events by interacting with the oncogene c-Myc. In searching for novel AP-2alpha- interacting factors, using an affinity chromatography approach, we have observed that oncoprotein DEK interacts with AP-2alpha in vitro. The existence of an interaction between AP-2alpha and DEK in cellular cultures was demonstrated by expression of a tagged AP-2alpha form followed by immunodetection. By transient co-expression experiments using a reporter for APOE promoter activity we have found that DEK stimulates the transactivation activity of AP-2alpha over APOE promoter. Finally, electrophoretic mobility shift assays suggested that DEK enhances the DNA-binding activity of AP-2alpha. Our data suggest a novel cellular function of DEK as a transcriptional co-activator.
机译:细胞分化和发育是转录水平上高度调控的过程。调节这些过程的主要转录因子之一是AP-2alpha,AP-2alpha是脊椎动物发育和胚胎发生所需的细胞类型特异性蛋白。 AP-2alpha还通过与癌基因c-Myc相互作用来调节细胞凋亡和细胞周期特异性事件。在使用亲和色谱法搜索新型AP-2alpha相互作用因子时,我们已经观察到癌蛋白DEK在体外与AP-2alpha相互作用。 AP-2alpha和DEK在细胞培养物中相互作用的存在通过标记的AP-2alpha形式的表达随后进行免疫检测来证明。通过使用APOE启动子活性的报道基因的瞬时共表达实验,我们发现DEK刺激AP-2alpha超过APOE启动子的反式激活活性。最后,电泳迁移率变动分析表明DEK增强了AP-2alpha的DNA结合活性。我们的数据表明DEK作为转录共激活因子的新型细胞功能。

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