Kirchhoff S, Wilhelm D, Angel P, Hauser H
Department of Gene Regulation and Differentiation, National Research Center for Biotechnology, Braunschweig, Germany.
Eur J Biochem. 1999 Apr;261(2):546-54. doi: 10.1046/j.1432-1327.1999.00308.x.
The interferon regulatory factor 1 (IRF-1) acts as a transcriptional inducer of the interferon beta (IFN-beta) gene and interferon-stimulated genes. Here we report that IRF-1-mediated IFN-beta induction depends on NFkappaB activity. IRF-1 by itself initiates NFkappaB activation by inducing a reduction in cellular MAD3/IkappaBalpha, an inhibitor of NFkappaB. After nuclear translocation, NFkappaB synergizes with IRF-1 on the cis-elements positive regulatory domain (PRD)II and PRDI/III to induce transcription of the IFN-beta gene. In contrast with IFN-beta transcription induced by dsRNA or virus, c-Jun/ATF-2 binding to PRDIV is not involved. Recombinant MAD3/IkappaBalpha is phosphorylated in vitro by extracts from IRF-1-expressing cells. IRF-1-dependent MAD3/IkappaBalpha degradation is not detectable in cells expressing a dominant negative mutant of the protein kinase PKR, suggesting that PKR mediates MAD3/IkappaBalpha degradation.
干扰素调节因子1（IRF-1）作为干扰素β（IFN-β）基因和干扰素刺激基因的转录诱导因子。在此我们报告，IRF-1介导的IFN-β诱导依赖于核因子κB（NFκB）活性。IRF-1自身通过诱导细胞内MAD3/IκBα（NFκB的一种抑制剂）减少来启动NFκB激活。核转位后，NFκB与IRF-1在顺式元件正调控区（PRD）II和PRDI/III上协同作用，以诱导IFN-β基因的转录。与双链RNA或病毒诱导的IFN-β转录不同，c-Jun/ATF-2与PRDIV的结合不参与其中。重组MAD3/IκBα在体外被表达IRF-1的细胞提取物磷酸化。在表达蛋白激酶PKR显性负性突变体的细胞中，未检测到IRF-1依赖的MAD3/IκBα降解，这表明PKR介导MAD3/IκBα降解。
