A NUCLEAR FACTOR FOR IL-6 EXPRESSION (NF-IL6) IS A MEMBER OF A C/EBP FAMILY

A NUCLEAR FACTOR FOR IL-6 EXPRESSION (NF-IL6) IS A MEMBER OF A C/EBP FAMILY
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DOI:
10.1002/j.1460-2075.1990.tb08316.x
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发表时间:
1990-06-01
期刊:
影响因子:
11.4
通讯作者:
KISHIMOTO, T
KISHIMOTO, T
中科院分区:
生物学1区
文献类型:
--
作者:
AKIRA, S;ISSHIKI, H;KISHIMOTO, T

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nf - IL-6是一种特异性结合IL-6基因中il - 1应答元件的核因子。本研究通过直接筛选.lambda克隆了NF-IL6的编码基因。使用NF-IL6结合序列作为配体的gt11文库。全长cDNA编码了一个345个氨基酸的蛋白质,具有潜在的亮氨酸拉链结构,并在C端与肝脏特异性转录因子C/EBP高度同源。在C/EBP的情况下,细菌融合蛋白与CCAAT同源性以及病毒增强子核心序列结合。重组NF-IL6以序列特异性的方式激活人IL-6启动子。Southern blot分析表明,NF-IL6基因通过进化具有高度保守性,并且存在几个共享dna结合域的其他相关基因。NF-IL6 mRNA在正常情况下不表达,但在LPS、IL-1或il - 6的刺激下被诱导。有趣的是,研究显示NF-IL6可以结合多种急性期蛋白基因和TNF、IL-8和G-CSF等其他细胞因子基因的调控区域,这意味着NF-IL6不仅可以调控IL-6基因,还可以调控参与急性期反应、炎症和造血的其他几个基因。
NF-IL6 is a nuclear factor that specifically binds to an IL1-responsive element in the IL-6 gene. In this study the gene encoding NF-IL6 has been cloned by direct screening of a .lambda.gt11 library using NF-IL6 binding sequence as a ligand. The full-length cDNA encoded a 345 amino acid protein with a potential leucine zipper structure and revealed a high degree of homology to a liver-specific transcriptional factor, C/EBP, at the C-terminal portion. The bacterial fusion protein bound to the CCAAT homology as well as the viral enhancer core sequences as in the case of C/EBP. Recombinant NF-IL6 activated the human IL-6 promoter in a sequence-specific manner. Southern blot analysis demonstrated the high-degree conservation of the NF-IL6 gene through evolution and the existence of several other related genes sharing the DNA-binding domain. NF-IL6 mRNA was normally not expressed, but induced by the stimulation with either LPS, IL-1 or IL6. Interestingly, NF-IL6 was shown to bind to the regulatory regions for various acute-phase protein genes and several other cytokine genes such as TNF, IL-8 and G-CSF, implying that NF-IL6 has a role in regulation not only for the IL-6 gene but also for several other genes involved in acute-phase reaction, inflammation and hemopoiesis.