Interferon regulatory factor 1 (IRF-1) mediates cell growth inhibition by transactivation of downstream target genes

作者：Sabine Kirchhoff, Fred Schaper, H. Häuser · 发表于：Nucleic Acids Research · 年份：1993 · DOI：10.1093/nar/21.12.2881 · 被引用次数：141 · 研究领域：Cytokine Signaling Pathways and Interactions、interferon and immune responses、Estrogen and related hormone effects

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.