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首页> 外文期刊>Molecular and Cellular Biology >Identification of a novel interleukin-6 response element containing an Ets-binding site and a CRE-like site in the junB promoter.
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Identification of a novel interleukin-6 response element containing an Ets-binding site and a CRE-like site in the junB promoter.

机译:鉴定在junB启动子中包含Ets结合位点和CRE样位点的新型白介素6反应元件。

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Interleukin-6 (IL-6) activation of the immediate-early gene junB has been shown to require both a tyrosine kinase and an unknown 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7)-sensitive pathway. Here we report the identification and characterization of an IL-6 immediate-early response element in the junB promoter (designated JRE-IL6) in HepG2 cells. The JRE-IL6 element, located at -149 to -124, contains two DNA motifs, an Ets-binding site (EBS) (CAGGAAGC) and a CRE-like site (TGACGCGA). Functional studies using variously mutated JRE-IL6 elements showed that both motifs were necessary and sufficient for IL-6 response of the promoter. The EBS of the JRE-IL6 element (JEBS) appears to bind a protein in the Ets family or a related protein which could also form a major complex with the EBSs of the murine sarcoma virus long terminal repeat or human T-cell leukemia virus type 1 long terminal repeat. The CRE-like site appears to weakly bind multiple CREB-ATF family proteins. Despite the similarity in the structure between the JRE-IL6 element and the polyomavirus enhancer PyPEA3, composed of an EBS and an AP1-binding site and known to be activated by a variety of oncogene signals, JRE-IL6 could not be activated by activated Ha-Ras, Raf-1, or 12-O-tetradecanoylphorbol-13-acetate. We show that IL-6 activates JRE-IL6 through an H7-sensitive pathway that does not involve protein kinase C, cyclic AMP-dependent kinase, Ca(2+)- or calmodulin-dependent kinases, Ras, Raf-1, or NF-IL6 (C/EBP beta). The combination of JEBS and the CRE-like site appears to form the basis for the selective and efficient response of JRE-IL6 to IL-6 signals, but not to signals generated by activated Ha-Ras, Raf-1, or protein kinase C.
机译:已经显示,立即早期基因junB的白介素6(IL-6)激活需要酪氨酸激酶和未知的1-(5-异喹啉磺酰基)-2-甲基哌嗪(H7)敏感途径。在这里,我们报告了HepG2细胞中junB启动子(称为JRE-IL6)中IL-6立即早期反应元件的鉴定和表征。位于-149至-124的JRE-IL6元件包含两个DNA基序,一个Ets结合位点(EBS)(CAGGAAGC)和一个CRE样位点(TGACGCGA)。使用各种突变的JRE-IL6元件的功能研究表明,两个基序对于启动子的IL-6应答都是必需的和充分的。 JRE-IL6元件的EBS(JEBS)似乎与Ets家族中的蛋白质或相关蛋白质结合,该蛋白质也可能与鼠肉瘤病毒长末端重复序列或人T细胞白血病病毒类型的EBS形成主要复合体1个长终端重复。 CRE样位点似乎弱结合多个CREB-ATF家族蛋白。尽管JRE-IL6元件和由EBS和AP1结合位点组成的多瘤病毒增强剂PyPEA3之间的结构相似,并且已知可被多种癌基因信号激活,但JRE-IL6不能被激活的Ha激活。 -Ras,Raf-1或12-O-十四烷酰佛波醇13-乙酸酯。我们表明,IL-6通过不涉及蛋白激酶C,环状AMP依赖性激酶,Ca(2+)或钙调蛋白依赖性激酶,Ras,Raf-1或NF的H7敏感途径激活JRE-IL6。 -IL6(C / EBP beta)。 JEBS和CRE样位点的结合似乎形成了JRE-IL6对IL-6信号的选择性和有效反应的基础,但对由活化的Ha-Ras,Raf-1或蛋白激酶C产生的信号却没有响应。

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