Kennedy G C, Rutter W J
Hormone Research Institute, University of California, San Francisco 94143-0534.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11498-502. doi: 10.1073/pnas.89.23.11498.
Purine-rich stretches of nucleotides (GAGA boxes) are often found just upstream of transcription start sites in many genes, including insulin. Mutational analysis suggests that the GAGA box plays an important role in transcription of the rat insulin I gene. We identify here at least four different proteins that bind specifically to the insulin GAGA box. Using a GAGA oligonucleotide, we have isolated a cDNA encoding a sequence-specific protein from a HIT (hamster insulinoma cell line) lambda gt11 library. This protein, which we designate Pur-1 (for purine binding), binds to the GAGA boxes of the rat insulin I and II genes and the human islet amyloid polypeptide gene. Pur-1 is a potent transactivator in both pancreatic and nonpancreatic cells. Furthermore, Pur-1 is able to activate an intact insulin promoter in HeLa cells, where it is normally inactive.
富含嘌呤的核苷酸片段（GAGA 框）常出现在包括胰岛素基因在内的许多基因转录起始位点的上游。突变分析表明，GAGA 框在大鼠胰岛素 I 基因的转录中起重要作用。我们在此鉴定出至少四种与胰岛素 GAGA 框特异性结合的不同蛋白质。利用一个 GAGA 寡核苷酸，我们从仓鼠胰岛素瘤细胞系（HIT）的 λgt11 文库中分离出一个编码序列特异性蛋白质的 cDNA。这种蛋白质，我们命名为 Pur-1（嘌呤结合蛋白），它能与大鼠胰岛素 I 和 II 基因以及人胰岛淀粉样多肽基因的 GAGA 框结合。Pur-1 在胰腺细胞和非胰腺细胞中都是一种有效的反式激活因子。此外，Pur-1 能够在通常无活性的 HeLa 细胞中激活完整的胰岛素启动子。
