IDENTIFICATION OF A MEMBER OF THE INTERFERON REGULATORY FACTOR FAMILY THAT BINDS TO THE INTERFERON-STIMULATED RESPONSE ELEMENT AND ACTIVATES EXPRESSION OF INTERFERON-INDUCED GENES
IDENTIFICATION OF A MEMBER OF THE INTERFERON REGULATORY FACTOR FAMILY THAT BINDS TO THE INTERFERON-STIMULATED RESPONSE ELEMENT AND ACTIVATES EXPRESSION OF INTERFERON-INDUCED GENES
复制标题
DOI：
10.1073/pnas.92.25.11657
复制
发表时间：
1995-12-05
影响因子：
11.1
通讯作者：
PITHA, PM
中科院分区：
文献类型：
--
作者：
AU, WC;MOORE, PA;PITHA, PM
干扰素调节因子家族在干扰素基因转录和干扰素刺激基因转录中起着重要作用。我们报告了IRF家族的一个成员的鉴定，我们将其命名为IRF-3。IRF-3基因以单拷贝形式存在于人类基因组DNA中。它在多种组织中有成分地表达，在病毒感染或干扰素处理的细胞中没有观察到相对稳定的IRF-3mRNA水平的增加。IRF-3基因编码一个50 kDa的蛋白，可与干扰素刺激的反应元件(ISRE)特异结合，但不能与IRF-1结合位点Prd-I结合。IRF-3的过表达可刺激干扰素刺激基因15(ISG15)启动子的表达，含有ISRE的启动子小鼠IFNA4启动子不受IRF-3诱导，可由LRF-1或病毒感染诱导。IRF-3作为Gal4融合蛋白的表达不能激活包含Gal4结合位点重复序列的氯霉素乙酰转移酶报告基因的表达，这表明该蛋白不包含转录反式激活结构域，IRF-3与ISG因子3伽马多肽(ISGF3 Gamma)之间的氨基酸同源性以及它们相似的结合特性表明，IRF-3可能与其他转录因子(可能是STAT家族的成员)形成复合体来激活转录。鉴定这个ISRE结合蛋白可能有助于我们理解不同STAT途径中的特异性。
A family of interferon (IFN) regulatory factors (IRFs) have been shown to play a role in transcription of IFN genes as well as IFN-stimulated genes. We report the identification of a member of the IRF family which we have named IRF-3. The IRF-3 gene is present in a single copy in human genomic DNA. It is expressed constitutively in a variety of tissues and no increase in the relative steady-state levels of IRF-3 mRNA was observed in virus-infected or IFN-treated cells. The IRF-3 gene encodes a 50-kDa protein that binds specifically to the IFN-stimulated response element (ISRE) but not to the IRF-1 binding site PRD-I, Overexpression of IRF-3 stimulates expression of the IFN-stimulated gene 15 (ISG15) promoter, an ISRE-containing promoter, The murine IFNA4 promoter, which can be induced by LRF-1 or viral infection, is not induced by IRF-3. Expression of IRF-3 as a Gal4 fusion protein does not activate expression of a chloramphenicol acetyltransferase reporter gene containing repeats of the Gal4 binding sites, indicating that this protein does not contain the transcription transactivation domain, The high amino acid homology between IRF-3 and ISG factor 3 gamma polypeptide (ISGF3 gamma) and their similar binding properties indicate that, like ISGF3 gamma, IRF-3 may activate transcription by complex formation with other transcriptional factors, possibly members of the Stat family. Identification of this ISRE-binding protein may help us to understand the specificity in the various Stat pathways.