Kinoshita S, Akira S, Kishimoto T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1473-6. doi: 10.1073/pnas.89.4.1473.
Using a DNA probe from the DNA-binding portion of the NF-IL6 gene and an antibody against the DNA-binding domain of NF-IL6, we isolated a gene homologous to NF-IL6 in the DNA-binding and leucine zipper domains. This intronless gene, termed NF-IL6 beta encodes a 269-amino acid protein with a potential leucine zipper structure, and the gene product can bind to the CCAAT homology as well as the viral enhancer core sequence, as in the cases of NF-IL6 and C/EBP. This gene is expressed at an undetectable or a minor level in normal tissues but is induced by lipopolysaccharide or inflammatory cytokines, as in the case of NF-IL6. NF-IL6 beta easily forms a heterodimer with NF-IL6 in vitro and the heterodimeric complex binds to the same DNA sequence as the respective homodimers. When examined by transient luciferase assays, NF-IL6 beta is consistently a stronger transactivator than NF-IL6. Furthermore, NF-IL6 beta shows a synergistic transcriptional effect with NF-IL6. These data suggest that NF-IL6 beta is an important transcriptional activator in addition to NF-IL6 in regulation of the genes involved in the immune and inflammatory responses.
利用来自NF-IL6基因DNA结合部分的DNA探针和针对NF-IL6 DNA结合结构域的抗体，我们在DNA结合和亮氨酸拉链结构域中分离出一个与NF-IL6同源的基因。这个无内含子基因，称为NF-IL6β，编码一种具有潜在亮氨酸拉链结构的269个氨基酸的蛋白质，并且该基因产物能够像NF-IL6和C/EBP那样，与CCAAT同源序列以及病毒增强子核心序列结合。该基因在正常组织中表达水平极低或几乎不表达，但像NF-IL6一样，可被脂多糖或炎性细胞因子诱导表达。NF-IL6β在体外很容易与NF-IL6形成异源二聚体，并且该异源二聚体复合物与各自同源二聚体结合相同的DNA序列。通过瞬时荧光素酶检测发现，NF-IL6β始终是比NF-IL6更强的转录激活因子。此外，NF-IL6β与NF-IL6表现出协同转录效应。这些数据表明，在免疫和炎症反应相关基因的调控中，NF-IL6β除了NF-IL6之外，也是一种重要的转录激活因子。
