Innate immune responses in NF-κB-repressing factor-deficient mice
Innate immune responses in NF-κB-repressing factor-deficient mice
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DOI：
10.1128/mcb.26.1.293-302.2006
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发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Hauser, H
中科院分区：
文献类型：
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作者：
Froese, N;Schwarzer, M;Hauser, H
NF-κ B抑制因子（NRF）是一种转录沉默子蛋白，其通过直接结合特定的邻近DNA序列来特异性地抵消几种NF-κ B依赖性启动子的基础活性。在细胞培养实验中，NRF mRNA的减少导致β干扰素、白细胞介素-8和诱导型一氧化氮合酶转录的去抑制。位于X染色体的单拷贝NRF基因广泛表达，编码690个氨基酸的蛋白质。N-末端部分包含核定位信号、DNA结合结构域和NF-κ B抑制结构域，而C-末端部分负责双链RNA结合和核仁定位。为了研究NRF在系统环境中的功能，创建了缺乏NRF基因的转基因小鼠。与体外实验的预测相反，NRF基因缺失的小鼠是可行的，并且具有与野生型小鼠无法区分的表型，即使在用不同病原体攻击后也是如此。数据暗示NRF的意外功能冗余。
NF-kappa B-repressing factor (NRF) is a transcriptional silencer protein that specifically counteracts the basal activity of several NF-kappa B-dependent promoters by direct binding to specific neighboring DNA sequences. In cell culture experiments, the reduction of NRF mRNA leads to a derepression of beta interferon, interleukin-8, and inducible nitric oxide synthase transcription. The X chromosome-located single-copy NRF gene is ubiquitously expressed and encodes a protein of 690 amino acids. The N-terminal part contains a nuclear localization signal, the DNA-binding domain, and the NF-kappa B-repressing domain, while the C-terminal part is responsible for double-stranded RNA binding and nucleolar localization. To study the function of NRF in a systemic context, transgenic mice lacking the NRF gene were created. Against predictions from in vitro experiments, mice with a deletion of the NRF gene are viable and have a phenotype that is indistinguishable from wild-type mice, even after challenge with different pathogens. The data hint towards an unexpected functional redundancy of NRF.