Poli V, Mancini F P, Cortese R
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Cell. 1990 Nov 2;63(3):643-53. doi: 10.1016/0092-8674(90)90459-r.
We analyzed a family of proteins from hepatoma cell nuclei that bind to interleukin-6 responsive elements (IL-6REs) of several acute-phase genes. This family is characterized by leucine zipper domains compatible with that of the CCAAT/enhancer binding protein (C/EBP). A cDNA clone coding for a member of the family, IL-6DBP, was isolated; it is strongly homologous to C/EBP in the region of the basic domain and in the leucine zipper sequence. IL-6DBP and C/EBP can interact in vitro to form heterodimers that bind to DNA with the same specificity as the respective homodimers, and they can interact functionally in vivo. Both the DNA binding activity and the trans-activating capacity of IL-6DBP are induced in hepatoma cells by treatment with IL-6 through a posttranslational mechanism, implicating it as a nuclear target of IL-6 and as a mediator of the IL-6-dependent transcriptional activation of liver genes during the acute-phase response.
我们分析了来自肝癌细胞核的一类蛋白质，这类蛋白质可与多个急性期基因的白细胞介素-6反应元件（IL-6REs）结合。该蛋白家族的特征是具有与CCAAT/增强子结合蛋白（C/EBP）的亮氨酸拉链结构域相匹配的结构域。我们分离出了编码该家族成员IL-6DBP的cDNA克隆；它在碱性结构域区域和亮氨酸拉链序列上与C/EBP高度同源。IL-6DBP和C/EBP在体外可相互作用形成异源二聚体，该异源二聚体与各自同源二聚体结合DNA的特异性相同，并且它们在体内也可发生功能性相互作用。通过翻译后机制，用IL-6处理肝癌细胞可诱导IL-6DBP的DNA结合活性和反式激活能力，这表明它是IL-6的核靶点，也是急性期反应期间肝脏基因IL-6依赖性转录激活的介质。
