Genetic analysis of NF-κB/Rel transcription factors defines functional specificities
Genetic analysis of NF-κB/Rel transcription factors defines functional specificities
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DOI：
10.1093/emboj/cdg534
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发表时间：
2003-10-15
期刊：
影响因子：
11.4
通讯作者：
Baltimore, D
中科院分区：
文献类型：
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作者：
Hoffmann, A;Leung, TH;Baltimore, D
NF-κ B转录因子由Rel同源家族的二聚体蛋白组成。它们激活许多含有高度不同kappaB位点序列的启动子。我们已经产生了缺乏单个和多个NF-κ B蛋白的细胞系，并使用它们来建立NF-κ B-IkappaB信号系统的组分之间的相互作用。二聚体家族内的功能补偿在敲除细胞系中是明显的。瞬时转染基因的分析给人的印象是滥交的内源基因的分析没有得到证实。使用TNF α作为诱导剂，一组内源性基因显示出广泛的亚基特异性以及高度可变的诱导动力学。比较基因的功能和亚基特异性与kappaB DNA结合位点的序列，我们发现几乎没有相关性，表明NF-κ B家族成员对内源性启动子的特异性不仅仅是由kappaB位点序列本身编码的。
The NF-kappaB transcription factors consist of dimeric proteins of the Rel homology family. They activate many promoters containing highly divergent kappaB-site sequences. We have generated cell lines lacking individual and multiple NF-kappaB proteins and used them to establish interactions between components of the NF-kappaB-IkappaB signaling system. Functional compensation within the family of dimers was evident in knockout cell lines. Analysis of transiently transfected genes gave an impression of promiscuity that was not borne out by analysis of endogenous genes. Using TNFalpha as an inducer, a panel of endogenous genes showed a wide range of subunit specificities as well as highly variable kinetics of induction. Comparing the function and subunit specificity of genes with the sequence of the kappaB DNA-binding site we found little correlation, indicating that NF-kappaB family member specificity for endogenous promoters is not solely encoded by the kappaB site sequence itself.