Araki E, Kahn C R, Shichiri M
Department of Metabolic Medicine, Kumamoto University School of Medicine.
Nihon Rinsho. 1994 Oct;52(10):2659-64.
IRS-1 (insulin receptor substrate-1) is a major substrate of the insulin receptor. Rat and human IRS-1 cDNAs, and human and mouse IRS-1 genes have been cloned so far. They show high homology in nucleic acids and amino acids levels, which indicate the high conservation of IRS-1 across the species. Interestingly, the entire coding region is contained in the 1st exon in the IRS-1 gene. The promoter of the mouse IRS-1 gene lacks TATA and CAAT boxes but contains 9 potential Spl binding sites, indicating that IRS-1 is a "housekeeping" gene. By deletion analysis, two positively and two negatively regulating fragments are identified in the promoter. In cultured adipocytes, insulin and dexamethasone down regulate IRS-1 expression by different mechanisms. Insulin down regulates at the post-translational level by shortening the protein half life, and dexamethasone down regulates at the post-transcriptional level mainly by shortening the mRNA half life.
胰岛素受体底物-1（IRS-1）是胰岛素受体的主要底物。目前已克隆出大鼠和人类的IRS-1 cDNA，以及人类和小鼠的IRS-1基因。它们在核酸和氨基酸水平上显示出高度同源性，这表明IRS-1在物种间具有高度保守性。有趣的是，IRS-1基因的整个编码区都包含在第1外显子中。小鼠IRS-1基因的启动子缺乏TATA盒和CAAT盒，但含有9个潜在的Sp1结合位点，这表明IRS-1是一个“管家”基因。通过缺失分析，在启动子中鉴定出两个正向调节片段和两个负向调节片段。在培养的脂肪细胞中，胰岛素和地塞米松通过不同机制下调IRS-1的表达。胰岛素通过缩短蛋白质半衰期在翻译后水平下调，地塞米松主要通过缩短mRNA半衰期在转录后水平下调。
