Al-Quobaili Faizeh, Montenarh Mathias
Medical Biochemistry and Molecular Biology, University of the Saarland, D-66424 Homburg, Germany.
Int J Mol Med. 2008 Apr;21(4):399-404.
The homeobox domain transcription factor PDX-1 is essential for pancreatic development and for the maintenance of beta-cell function. The participation of pancreatic duodenal homeobox factor-1 (PDX-1) in the transcription of several genes which are essential for glucose sensing and insulin synthesis underlines its key role in beta-cells of the pancreas. PDX-1 binds to the promoter of insulin, glucose transporter 2, and glucokinase and regulates their expression. By protein-protein interaction, PDX-1 acts in concert with other transcription factors or coactivators at the level of the insulin promoter. Ectopic expression of PDX-1 together with other cofactors can re-program cells to behave like beta-cells and produce insulin. This property of PDX-1 opens new strategies for the treatment of diabetes. Little is known about its regulation at the posttranslational level. Here, we report on its DNA-binding activity, the nuclear import and on post-translational modifications such as phosphorylation, glycosylation and sumoylation. Modulation of these post-translational modifications may be an alternate strategy for treating diabetes.
同源框结构域转录因子PDX-1对胰腺发育和β细胞功能的维持至关重要。胰腺十二指肠同源框因子-1（PDX-1）参与了几个对葡萄糖感知和胰岛素合成至关重要的基因的转录，这突出了其在胰腺β细胞中的关键作用。PDX-1与胰岛素、葡萄糖转运蛋白2和葡萄糖激酶的启动子结合并调节它们的表达。通过蛋白质-蛋白质相互作用，PDX-1在胰岛素启动子水平上与其他转录因子或共激活因子协同作用。PDX-1与其他辅助因子的异位表达可使细胞重新编程，使其表现得像β细胞并产生胰岛素。PDX-1的这一特性为糖尿病的治疗开辟了新策略。人们对其翻译后水平的调控知之甚少。在此，我们报告其DNA结合活性、核输入以及磷酸化、糖基化和类泛素化等翻译后修饰。对这些翻译后修饰的调节可能是治疗糖尿病的另一种策略。
