Campillos Mónica, García Miguel Angel, Valdivieso Fernando, Vázquez Jesús
Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, 28049 Cantoblanco, Madrid, Spain.
Nucleic Acids Res. 2003 Mar 1;31(5):1571-5. doi: 10.1093/nar/gkg247.
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.
细胞分化和发育是转录水平上受到高度调控的过程。调控这些过程的主要转录因子之一是AP-2α,它是脊椎动物发育和胚胎发生所必需的细胞类型特异性蛋白。AP-2α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。在寻找新型AP-2α相互作用因子的过程中,我们采用亲和层析方法观察到癌蛋白DEK在体外与AP-2α相互作用。通过表达带标签的AP-2α形式并随后进行免疫检测,证实了细胞培养物中AP-2α与DEK之间存在相互作用。通过使用APOE启动子活性报告基因的瞬时共表达实验,我们发现DEK刺激AP-2α对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-2α的DNA结合活性。我们的数据表明DEK作为转录共激活因子具有一种新的细胞功能。