PUR-1, A ZINC-FINGER PROTEIN THAT BINDS TO PURINE-RICH SEQUENCES, TRANSACTIVATES AN INSULIN PROMOTER IN HETEROLOGOUS CELLS

PUR-1, A ZINC-FINGER PROTEIN THAT BINDS TO PURINE-RICH SEQUENCES, TRANSACTIVATES AN INSULIN PROMOTER IN HETEROLOGOUS CELLS
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DOI:
10.1073/pnas.89.23.11498
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发表时间:
1992-12-01
影响因子:
11.1
通讯作者:
RUTTER, WJ
RUTTER, WJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KENNEDY, GC;RUTTER, WJ

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富含嘌呤的核苷酸片段(GAGA盒)通常位于许多基因转录起始点的上游,包括胰岛素。突变分析表明,GagA盒在大鼠胰岛素I基因转录中起重要作用。我们在这里鉴定了至少四种不同的蛋白质,它们专门与胰岛素Gaga盒结合。使用GagA寡核苷酸,我们从HIT(仓鼠胰岛素瘤细胞系)lambdagt11文库中分离到编码序列特异性蛋白的cDNA。这种蛋白,我们将其命名为PUR-1(用于嘌呤结合),与大鼠胰岛素I和II基因以及人类胰岛淀粉样多肽基因的Gaga盒结合。PUR-1在胰腺和非胰腺细胞中都是一种有效的反式激活因子。此外,PUR-1能够激活HeLa细胞中一个完整的胰岛素启动子,而在HeLa细胞中它通常是不活跃的。
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) lambdagt11 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.