...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >Decreased expression and activity of the immediate-early growth response (Egr-1) gene product during cellular senescence.
【24h】

Decreased expression and activity of the immediate-early growth response (Egr-1) gene product during cellular senescence.

机译：表达和活性的下降即早期生长反应(Egr-1)基因产品在细胞衰老。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Human diploid fibroblasts (HDFs) undergo a limited number of population doublings in culture before reaching the end of their proliferative life span, an event termed in vitro cellular senescence. Considerable evidence suggests that altered expression of key genes involved in the mitogenic response may be responsible for the inability of senescent cells to proliferate. Here we examined the expression and activity of the early growth response-1 (egr-1) gene, an "immediate-early" gene that is believed to link extracellular mitogenic signals to cell-cycle progression. We found that egr-1 was strongly downregulated in senescent HDFs at the level of mRNA, protein, and DNA binding activity. Decreased DNA binding activity of Egr-1 in vitro corresponded to decreased transcriptional activation in vivo. To further understand the mechanism of egr-1 downregulation, we examined the potential role of the serum response elements (SREs) present in the egr-1 promoter. Electrophoretic mobility shift studies using young and old cell nuclear extracts showed a marked decrease in serum response factor (SRF) binding activity to the SRE in old compared to young cells. Loss of SRF binding activity has been correlated with the loss of expression of another growth-related immediate-early gene (c-fos). These results suggest a common mechanism for the downregulation of c-fos, egr-1, and other SRE-dependent, mitogen-responsive genes during cellular senescence.
机译：人类二倍体成纤维细胞(HDFs)进行限制文化的人口倍增达到增生性生活的结束,一个事件称为体外细胞衰老。改变的关键基因的表达促有丝分裂的响应可能负责衰老细胞增殖的无能。我们检查的表达式和活动早期增长response-1 (egr-1)基因“即早期基因被认为链接细胞外促有丝分裂的细胞循环信号进展。在衰老HDFs的表达下调信使rna、蛋白质和DNA结合活性。Egr-1体外的DNA结合活性下降与减少转录激活体内。我们检查了,差别egr-1对这些机制血清反应的潜在作用的元素(sr) egr-1启动子中。电泳迁移率改变研究使用年轻和年老细胞核提取显示显著降低血清反应因子(SRF)绑定活动相比旧的行为年轻的细胞。与表达的损失另一个与生长有关的基因即早期(c-fos)。c-fos,差别的对这些egr-1等在SRE-dependent, mitogen-responsive基因细胞衰老。

著录项

相似文献

  • 外文文献
  • 中文文献
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