Cooke D W, Lane M D
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-2520, USA.
J Biol Chem. 1999 Apr 30;274(18):12917-24. doi: 10.1074/jbc.274.18.12917.
Insulin represses GLUT4 expression in 3T3-L1 adipocytes through an insulin response element located at bases -706 to -676 in the 5'-flanking sequence. Nuclear proteins related to the nuclear factor I (NF1) family of transcription factors bind to this insulin response element. Mutations that disrupt binding of NF1 proteins to the insulin response element impair the insulin response in reporter gene assays. Insulin treatment of 3T3-L1 adipocytes induces a rapid change in the level of phosphorylation of NF1 proteins, providing a potential mechanism for insulin's ability to regulate gene expression through NF1. Another as yet unidentified protein, not related to NF1, also binds to the GLUT4 insulin response element and is able to mediate partial repression of the GLUT4 promoter in reporter gene assays.
胰岛素通过位于5'侧翼序列中-706至-676碱基处的胰岛素反应元件抑制3T3-L1脂肪细胞中GLUT4的表达。与转录因子核因子I（NF1）家族相关的核蛋白与该胰岛素反应元件结合。破坏NF1蛋白与胰岛素反应元件结合的突变会损害报告基因检测中的胰岛素反应。用胰岛素处理3T3-L1脂肪细胞会导致NF1蛋白磷酸化水平迅速变化，这为胰岛素通过NF1调节基因表达的能力提供了一种潜在机制。另一种尚未鉴定的、与NF1无关的蛋白也与GLUT4胰岛素反应元件结合，并且在报告基因检测中能够介导GLUT4启动子的部分抑制。
