A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation
A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation
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DOI：
10.1101/gad.1329805
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发表时间：
2005-09-15
影响因子：
10.5
通讯作者：
Smale, ST
中科院分区：
文献类型：
--
作者：
Sanjabi, S;Williams, KJ;Smale, ST
NF-κ B家族成员p65（RelA）和c-Rel识别相似的DNA序列，但突变小鼠的表型表明，这些蛋白质调节不同的基因组。在这里，我们证明了46个独特的残基内的86个残基的Rel同源区（RHR）的c-Rel的片段负责的c-Rel的IL 12 b基因诱导的骨髓来源的巨噬细胞中的脂多糖的要求。这些相同的残基负责树突状细胞中IL 12 a诱导的c-Rel需求，并且在两种情况下，没有发现c-Rel特异性共激活剂相互作用的证据。（NF-κ B）识别序列是相同的，c-Rel的同源二聚体和含有关键c-Rel残基的嵌合p65蛋白的同源二聚体以高亲和力结合至更宽范围的NF-κ B。kappa B识别序列比野生型p65同源二聚体。这些结果表明，尽管具有相似的结合位点共有序列和DNA接触残基，但密切相关的转录因子家族成员的独特功能可以由以高亲和力识别的DNA序列范围的差异决定。
The NF-kappa B family members p65 (RelA) and c-Rel recognize similar DNA sequences, yet the phenotypes of mutant mice suggest that these proteins regulate distinct sets of genes. Here we demonstrate that 46 unique residues within an 86-residue segment of the Rel homology region (RHR) of c-Rel are responsible for the c-Rel requirement for Il12b gene induction by lipopolysaccharide in bone marrow-derived macrophages. These same residues were responsible for the c-Rel requirement for Il12a induction in dendritic cells, and in both instances, no evidence of c-Rel-specific coactivator interactions was found. Although the residues of c-Rel and p65 that contact specific bases and the DNA backbone within nuclear factor-kappa B (NF-kappa B) recognition sequences are identical, homodimers of c-Rel and of a chimeric p65 protein containing the critical c-Rel residues bound with high affinity to a broader range of NF-kappa B recognition sequences than did wild-type p65 homodimers. These results demonstrate that the unique functions of closely related transcription factor family members can be dictated by differences in the range of DNA sequences recognized at high affinity, despite having similar binding site consensus sequences and DNA contact residues.