Kirchhoff S, Schaper F, Hauser H
Genetics of Eukaryotes, GBF--Gesellschaft für Biotechnologische Forschung mbH, Braunschweig, Germany.
Nucleic Acids Res. 1993 Jun 25;21(12):2881-9. doi: 10.1093/nar/21.12.2881.
Interferon regulatory factor 1 (IRF-1) is a DNA-binding factor which recognizes regulatory elements in the promoters of interferon (IFN)-beta and some IFN-inducible genes. We observed that expression of transfected murine IRF-1 in different mammalian cell lines leads to down-regulation or stop of proliferation depending on the extent of expression. Expression of fusion proteins composed of IRF-1 and the hormone binding domain of the human estrogen receptor does not exhibit IRF-1 activity in the absence of estrogen. However, after estrogen treatment of the cells IFN-beta promoters are activated and the cells stop growing. As shown by expression of IRF-1 mutants both functions of the IRF-1-protein require DNA-binding and transcriptional activation. Since secreted factors including IFNs are not responsible for the anti-proliferative effect of IRF-1 we suggest that IRF-1 may be regarded as a negative regulator of cell growth which acts by activation of down-stream effector genes.
干扰素调节因子1(IRF-1)是一种DNA结合因子,可识别干扰素(IFN)-β及一些IFN诱导基因启动子中的调控元件。我们观察到,转染的小鼠IRF-1在不同哺乳动物细胞系中的表达会根据表达程度导致增殖下调或停止。在没有雌激素的情况下,由IRF-1和人雌激素受体的激素结合域组成的融合蛋白不表现出IRF-1活性。然而,在用雌激素处理细胞后,IFN-β启动子被激活,细胞停止生长。如IRF-1突变体的表达所示,IRF-1蛋白的两种功能都需要DNA结合和转录激活。由于包括IFN在内的分泌因子与IRF-1的抗增殖作用无关,我们认为IRF-1可被视为细胞生长的负调节因子,其通过激活下游效应基因发挥作用。