...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Epidermal Growth Factor Enhances Cellular TATA Binding Protein Levels and Induces RNA Polymerase I- and III-Dependent Gene Activity
【24h】

Epidermal Growth Factor Enhances Cellular TATA Binding Protein Levels and Induces RNA Polymerase I- and III-Dependent Gene Activity

机译：表皮生长因子提高细胞TATA结合蛋白水平，并诱导RNA聚合酶I和III依赖的基因活性。

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

摘要

TATA binding protein (TBP) is a central transcription factor used by all three cellular RNA polymerases. Changes in the levels of TBP have been shown to have selective effects on gene activity. Overexpression of TBP has been recently shown to contribute to cellular transformation, and elevated levels of TBP occur in a clinically significant proportion of human colon tumors relative to matched normal tissue. To understand the mechanisms by which TBP is regulated, we have analyzed whether activation of the epidermal growth factor receptor (EGFR), a membrane-bound tyrosine receptor kinase that is activated in a large number of human cancers, can serve to regulate cellular TBP. We show that treatment of mouse epidermal cells with EGF produces an increase in TBP levels, which can be blocked with an EGFR-specific inhibitor. In contrast, TBP levels remain unchanged after EGF treatment of EGFR null cells. EGF-mediated increases in TBP are regulated at the transcriptional level, as transient expression of the human TBP promoter is induced with EGF. This regulatory event is dependent upon the downstream activation of Ras and requires the activation of p38, JNK, and ERK mitogen-activated protein kinases. The consequence of elevated TBP on gene expression was further determined. Transcription by RNA polymerase (Pol) I and III was induced by EGF. Directly overexpressing TBP also stimulated transcription from these promoters. Thus, we have identified a new and important target of EGFR signaling, TBP, that contributes to EGF-mediated stimulation of RNA Pol I- and III-dependent gene activity. Since the cellular levels of the products of these genes, tRNAs and rRNAs, determine the translational capacity of cells, this event may be an important contributor to the transforming function of EGF.
机译：TATA结合蛋白（TBP）是所有三种细胞RNA聚合酶均使用的中央转录因子。已经显示TBP水平的变化对基因活性具有选择性作用。最近显示TBP的过表达有助于细胞转化，并且相对于匹配的正常组织，TBP的水平升高在临床上显着比例的人结肠肿瘤中发生。为了了解调节TBP的机制，我们分析了表皮生长因子受体（EGFR）（一种在许多人类癌症中被激活的膜结合酪氨酸受体激酶）的激活是否可以调节细胞TBP。我们显示，用表皮生长因子治疗小鼠表皮细胞可产生TBP水平升高，而该水平可被EGFR特异性抑制剂阻断。相反，EGF处理EGFR空细胞后，TBP水平保持不变。 EGF介导的TBP增加在转录水平受到调控，因为EGF诱导了人TBP启动子的瞬时表达。此调节事件取决于Ras的下游激活，并需要激活p38，JNK和ERK丝裂原激活的蛋白激酶。进一步确定了TBP升高对基因表达的影响。 EGF诱导RNA聚合酶（Pol）I和III的转录。直接过表达的TBP也刺激了这些启动子的转录。因此，我们已经确定了EGFR信号的新的重要靶标TBP，它有助于EGF介导的刺激RNA Pol I和III依赖的基因活性。由于这些基因，tRNA和rRNA产物的细胞水平决定了细胞的翻译能力，因此该事件可能是EGF转化功能的重要贡献者。

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