• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Induction of the mouse serum amyloid A3 gene by cytokines requires both C/EBP family proteins and a novel constitutive nuclear factor.
【24h】

Induction of the mouse serum amyloid A3 gene by cytokines requires both C/EBP family proteins and a novel constitutive nuclear factor.

机译：细胞因子诱导小鼠血清淀粉样蛋白A3基因既需要C / EBP家族蛋白，又需要一种新的组成型核因子。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Serum amyloid A (SAA) is a major acute-phase protein synthesized and secreted mainly by the liver. In response to acute inflammation, its expression may be induced up to 1,000-fold, primarily as a result of a 200-fold increase in the rate of SAA gene transcription. We have previously demonstrated that a 350-bp promoter fragment from the mouse SAA3 gene was necessary and sufficient to confer liver-specific and cytokine-induced expression. Deletion studies identified a distal response element that is responsible for the cytokine response and has properties of an inducible transcriptional enhancer. In this study, we further analyzed the distal response element and showed that it consists of three functionally distinct elements: the A element constitutes a weak binding site for C/EBP family proteins, the B element also interacts with C/EBP family proteins but with a much higher binding affinity, and the C element interacts with a novel constitutive nuclear factor, SEF-1. Site-specific mutation studies revealed that all three elements were required for maximum promoter activity. C/EBP alpha, C/EBP beta, and C/EBP delta were capable of interacting with elements A and B. Under noninduced conditions, C/EBP alpha was the major binding factor; however, upon cytokine stimulation C/EBP beta- and C/EBP delta-binding activities were dramatically increased and became the predominant binding factors. Consistent with these binding studies were the cotransfection experiments in which C/EBP beta and C/EBP delta were shown to be potent transactivators for the SAA3 promoter. Moreover, the transactivation required an intact B element despite the presence of other functional C/EBP-binding sites. Interestingly, although element C did not interact with C/EBP directly, it was nevertheless required for maximum transactivation by C/EBP delta. Our studies thus demonstrate that both C/EBP family proteins and SEF-1 are required to transactivate the SAA3 gene.
机译：血清淀粉样蛋白A（SAA）是一种主要由肝脏合成和分泌的主要急性期蛋白。响应急性炎症，其表达可能被诱导多达1,000倍，主要是SAA基因转录速率增加200倍的结果。我们以前已经证明，来自小鼠SAA3基因的350 bp启动子片段是必需的，并且足以赋予肝脏特异性和细胞因子诱导的表达。删除研究确定了远端反应元件，该元件负责细胞因子反应，并具有诱导型转录增强子的特性。在这项研究中，我们进一步分析了远端反应元件，并发现它由三个功能上不同的元件组成：A元件构成C / EBP家族蛋白的弱结合位点，B元件也与C / EBP家族蛋白相互作用，但与具有更高的结合亲和力，并且C元素与新型本构核因子SEF-1相互作用。位点特异性突变研究表明，所有三个要素都是启动子最大活性所必需的。 C / EBP alpha，C / EBP beta和C / EBP delta能够与元素A和B相互作用。在非诱导条件下，C / EBP alpha是主要的结合因子。然而，在细胞因子刺激下，C / EBPβ-和C / EBPδ-结合活性显着增加，并成为主要的结合因子。与这些结合研究一致的是共转染实验，其中C / EBP beta和C / EBP delta被证明是SAA3启动子的有效反式激活因子。此外，尽管存在其他功能性C / EBP结合位点，但反式激活仍需要完整的B元素。有趣的是，尽管元素C并未直接与C / EBP相互作用，但仍需要C / EBPδ最大反式激活。因此，我们的研究表明，C / EBP家族蛋白和SEF-1都是激活SAA3基因所必需的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号