Strehlow I, Seegert D, Frick C, Bange F C, Schindler C, Böttger E C, Decker T
Fraunhofer Institute for Toxicology and Molecular Biology, Hannover, Germany.
J Biol Chem. 1993 Aug 5;268(22):16590-5.
We have obtained genomic DNA encoding the interferon-gamma (IFN-gamma)-inducible IFP 53/tryptophanyl-tRNA synthetase. Comparison with several different IFP 53 cDNA clones revealed a complex pattern of alternatively spliced 5'-untranslated regions. The interferon-responsive region within the IFP 53 promoter was found to contain a gamma-interferon activation site (GAS) but not the interferon-stimulated response element and to bind the gamma-interferon activation factor (GAF). GAF.GAS complexes contained the IFN-regulated 91-kDa protein. Competition experiments defined the GAS boundaries and showed that GAF binding to the IFP 53 GAS could be prevented by an excess of the IFN-gamma response regions of several other IFN-gamma-inducible genes. We thus provide evidence for a central role of GAS.GAF in gene transcription mediated by IFN-gamma and suggest a consensus sequence defining more precisely the requirements for GAF binding to DNA.
我们已获得编码干扰素-γ（IFN-γ）诱导型IFP 53/色氨酰-tRNA合成酶的基因组DNA。与几个不同的IFP 53 cDNA克隆进行比较，发现了5'-非翻译区复杂的可变剪接模式。IFP 53启动子内的干扰素反应区域含有一个γ-干扰素激活位点（GAS），但不含有干扰素刺激反应元件，且能结合γ-干扰素激活因子（GAF）。GAF.GAS复合物包含IFN调节的91-kDa蛋白。竞争实验确定了GAS的边界，并表明过量的其他几个IFN-γ诱导基因的IFN-γ反应区域可阻止GAF与IFP 53 GAS的结合。因此，我们提供了证据证明GAS.GAF在IFN-γ介导的基因转录中起核心作用，并提出了一个更精确界定GAF与DNA结合要求的共有序列。
