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

Interferon regulatory factor 1 (IRF-1) mediates cell growth inhibition by transactivation of downstream target genes.
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干扰素调节因子 1 (IRF-1) 通过下游靶基因的反式激活来介导细胞生长抑制。

DOI:
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发表时间:
1993
影响因子:
14.9
通讯作者:
H. Hauser
H. Hauser
中科院分区:
生物学2区
文献类型:
--
作者:
S. Kirchhoff;F. Schaper;H. Hauser

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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 启动子和一些 IFN 诱导基因的调节元件。我们观察到,转染的鼠IRF-1在不同哺乳动物细胞系中的表达会导致增殖的下调或停止,具体取决于表达的程度。由IRF-1和人雌激素受体的激素结合结构域组成的融合蛋白的表达在没有雌激素的情况下不表现出IRF-1活性。然而,在雌激素处理细胞后,IFN-β启动子被激活,细胞停止生长。正如 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,因此我们认为 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。
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.