...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma.
【24h】

DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma.

机译：EWS-FLI-1融合蛋白的DNA结合和转录激活特性是由尤因肉瘤中的t（11; 22）易位引起的。

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

摘要

The 5' half of the EWS gene has recently been described to be fused to the 3' regions of genes encoding the DNA-binding domain of several transcriptional regulators, including ATF1, FLI-1, and ERG, in several human tumors. The most frequent occurrence of this situation results from the t(11;22)(q24;q12) chromosome translocation specific for Ewing sarcoma (ES) and related tumors which joins EWS sequences to the 3' half of FLI-1, which encodes a member of the Ets family of transcriptional regulators. We show here that this chimeric gene encodes an EWS-FLI-1 nuclear protein which binds DNA with the same sequence specificity as the wild-type parental FLI-1 protein. We further show that EWS-FLI-1 is an efficient sequence-specific transcriptional activator of model promoters containing FLI-1 (Ets)-binding sites, a property which is strictly dependent on the presence of its EWS domain. Comparison of the properties of the N-terminal activation domain of FLI-1 to those of the EWS domain of the fusion protein indicates that EWS-FLI-1 has altered transcriptional activation properties compared with FLI-1. These results suggest that EWS-FLI-1 contributes to the transformed phenotype of ES tumor cells by inducing the deregulated and/or unscheduled activation of genes normally responsive to FLI-1 or to other close members of the Ets family. ES and related tumors are characterized by an elevated level of c-myc expression. We show that EWS-FLI-1 is a transactivator of the c-myc promoter, suggesting that upregulation of c-myc expression is under control of EWS-FLI-1.
机译：EWS基因的5'半部分最近已被描述为与几种人类肿瘤中编码包括ATF1，FLI-1和ERG在内的几种转录调节因子的DNA结合结构域的基因的3'区域融合。这种情况最常见的发生是由于尤因肉瘤（ES）和相关肿瘤特异的t（11; 22）（q24; q12）染色体易位引起的，该染色体易位将EWS序列连接到FLI-1的3'一半，该序列编码Ets转录调节子家族的成员。我们在这里显示该嵌合基因编码EWS-FLI-1核蛋白，该蛋白结合具有与野生型亲本FLI-1蛋白相同的序列特异性的DNA。我们进一步表明，EWS-FLI-1是包含FLI-1（Ets）结合位点的模型启动子的有效序列特异性转录激活因子，该属性严格取决于其EWS域的存在。将FLI-1的N-末端激活结构域的性质与融合蛋白的EWS结构域的性质进行比较表明，与FLI-1相比，EWS-FLI-1具有改变的转录激活性质。这些结果表明，EWS-FLI-1通过诱导正常情况下对FLI-1或对Ets家族其他成员有响应的基因的失调和/或非计划性激活来促进ES肿瘤细胞的转化表型。 ES和相关肿瘤的特征在于c-myc表达水平升高。我们表明，EWS-FLI-1是c-myc启动子的反式激活因子，表明c-myc表达的上调受EWS-FLI-1的控制。

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