Genetics of Eukaryotes, GBF-Gesellschaft für Biotechnologische Forschung mbH, Mascheroder Weg 1, 38124, Braunschweig, Germany.
Cytotechnology. 1995 Jan;18(1-2):67-75. doi: 10.1007/BF00744321.
We have attempted to establish a system in which cell proliferation is controlled by a physiological regulator. Interferon regulatory factor 1 (IRF-1) is a transcription factor that recognizes a sequence which is present in the interferon-β promoter as well as in the promoters of interferon-inducible genes. IRF-1 acts as a tumor suppressor. Constitutive overexpression of recombinant IRF-1 leads to inhibition of cell growth. The extent of this growth arrest depends on the intracellular concentration of IRF-1. In order to allow IRF-1 expression in various mammalian cells we have established two different systems for conditional IRF-1 transcription and activation, respectively. In one case, an inducible promoter, in the other case a fusion protein composed of IRF-1 and the hormone-binding domain of the human estrogen receptor was used. Both systems allow to control gradually the growth of mammalian cell lines by adjusting the intracellular concentration of IRF-1 via estradiol or tetracycline in the medium. Despite the activity of IRF-1 as an antiproliferative agent the expression of certain proteins is retained. Moreover, expression of genes which are controlled by IRF-1 responsive promoters is enhanced.
我们试图建立一个系统，使细胞增殖受到生理调节剂的控制。干扰素调节因子 1（IRF-1）是一种转录因子，可识别存在于干扰素-β启动子以及干扰素诱导基因启动子中的序列。IRF-1 作为一种肿瘤抑制因子。重组 IRF-1 的组成型过表达导致细胞生长抑制。这种生长停滞的程度取决于细胞内 IRF-1 的浓度。为了在各种哺乳动物细胞中表达 IRF-1，我们分别建立了两种用于条件性 IRF-1 转录和激活的不同系统。一种情况下使用诱导型启动子，另一种情况下使用由 IRF-1 和人雌激素受体的激素结合域组成的融合蛋白。这两种系统都允许通过培养基中的雌二醇或四环素逐渐控制哺乳动物细胞系的生长，从而调节细胞内 IRF-1 的浓度。尽管 IRF-1 作为一种抗增殖剂具有活性，但某些蛋白质的表达仍然保留。此外，受 IRF-1 响应启动子控制的基因的表达增强。
