Structural and functional analysis of NF-kappa B. Determinants of DNA binding specificity and protein interaction.
Structural and functional analysis of NF-kappa B. Determinants of DNA binding specificity and protein interaction.
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DOI：
10.1016/s0021-9258(18)31615-6
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发表时间：
1994-12
期刊：
影响因子：
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通讯作者：
Roland;-M.;SchmidSQ;Susanne LiptayQn;Jonathan;-C.;Betts;Gary J. Nabelll
中科院分区：
文献类型：
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作者：
Roland;-M.;SchmidSQ;Susanne LiptayQn;Jonathan;-C.;Betts;Gary J. Nabelll
核因子-kappa B转录因子在Rel癌基因最初描述的区域显示出高度的序列保守性。两个家族成员，核因子-kappa B1和核因子-kappa B2，具有不同的DNA结合特性和对不同增强子的不同功能作用。例如，核因子-kappa B1与人类免疫缺陷病毒(HIV)的kappa B位点结合的亲和力大约是NF-kappa B2的15倍。在本研究中，我们定义了REL结构域中的区域，这些区域决定了DNA结合的特异性以及与其他蛋白质的相互作用。我们发现，核因子-kappa B1的COOH末端假定的REL二聚化结构域是优先结合HIV kappa B位点所必需的。相反，NF-kappa B2与relA(P65)对HIV增强子的优先刺激是由NF-kappa B2的NH2-和COOH-末端REL结构域决定的。核因子-kappa B2的这两个区域也介导了与Bcl3的优先协同作用。这些数据表明，REL保守区的一个特定亚域已经进化成控制DNA结合的精细特异性，并且REL结构域中的两个不同的亚区决定了与其他转录因子相互作用的特异性。因此，这些特定的Rel保守结构域决定了NF-kappa B相互作用的特异性，并有助于选择性地激活基因。
The NF-kappa B transcription factors display a high degree of sequence conservation in a domain initially described in the rel oncogene. Two family members, NF-kappa B1 and NF-kappa B2, have distinct DNA binding properties and functionally distinct effects on different enhancers. NF-kappa B1, for example, binds to the kappa B site from the human immunodeficiency virus (HIV) with approximately 15-fold higher affinity than NF-kappa B2. In this study, we have defined regions within the Rel domain which determine DNA binding specificity and interaction with other proteins. We find that the COOH-terminal putative Rel dimerization domain of NF-kappa B1 is required for preferential binding to the HIV kappa B site. In contrast, preferential stimulation of the HIV enhancer by NF-kappa B2 with RelA(p65) is determined by both the NH2- and COOH-terminal Rel domains of NF-kappa B2. These two regions of NF-kappa B2 also mediate preferential synergy with Bcl3. These data suggest that a specific subdomain of the Rel conserved region has evolved to control the fine specificity of DNA binding, and two distinct subregions within the Rel domain determine the specificity of interaction with other transcription factors. These specific Rel-conserved domains therefore determine the specificity of NF-kappa B interactions and contribute to selective gene activation.