Grant C E, Vasa M Z, Deeley R G
Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
Nucleic Acids Res. 1995 Jun 25;23(12):2137-46. doi: 10.1093/nar/23.12.2137.
In mammals, some of the effects of interferon (IFN) on gene transcription are known to be mediated by a family of IFN-inducible DNA-binding proteins, the IFN regulatory factor (IRF) family, which includes both activators and repressors of transcription. Although IFN activities have been described in many vertebrates, little is known about regulation of IFN- or IFN-stimulated genes in species other than human and mouse. Here, we report the cloning of a chicken cDNA, cIRF-3, encoding a protein with a DNA-binding domain similar to that found in the mammalian IRF family of proteins. Similarity between cIRF-3 and the mammalian IRFs is comparable with that between known members of the family. It is most similar to the IRF proteins ICSBP and ISGF3 gamma but is equally divergent from both. Gel mobility shift assays indicate that cIRF-3 is capable of binding a known IFN-stimulated response element that is conserved between the mammalian and chicken Mx genes. Expression of the cIRF-3 gene can be induced to high levels by poly(I).poly(C). Induction is rapid and transient with no requirement for protein synthesis. Co-treatment of cells with cycloheximide results in superinduction of cIRF-3 mRNA. The structural and regulatory characteristics of cIRF-3 indicate that it is the first example of a non-mammalian IRF protein.
在哺乳动物中,已知干扰素(IFN)对基因转录的一些影响是由一类IFN诱导的DNA结合蛋白介导的,即IFN调节因子(IRF)家族,该家族包括转录激活因子和抑制因子。虽然在许多脊椎动物中都描述了IFN活性,但对于人类和小鼠以外的物种中IFN或IFN刺激基因的调控知之甚少。在这里,我们报告了鸡cDNA(cIRF-3)的克隆,其编码一种蛋白质,该蛋白质具有与哺乳动物IRF家族蛋白质中发现的DNA结合结构域相似的结构域。cIRF-3与哺乳动物IRF之间的相似性与该家族已知成员之间的相似性相当。它与IRF蛋白ICSBP和ISGF3γ最为相似,但与两者的差异程度相同。凝胶迁移率变动分析表明,cIRF-3能够结合哺乳动物和鸡Mx基因之间保守的已知IFN刺激反应元件。cIRF-3基因的表达可以被聚肌苷酸-聚胞苷酸(poly(I).poly(C))诱导到高水平。诱导迅速且短暂,不需要蛋白质合成。用环己酰亚胺对细胞进行共处理会导致cIRF-3 mRNA的超诱导。cIRF-3的结构和调控特征表明它是非哺乳动物IRF蛋白的首个实例。