首页> 外文期刊>Molecular and Cellular Biology >Rapamycin Induces the G0 Program of Transcriptional Repression in Yeast by Interfering with the TOR Signaling Pathway
【24h】

Rapamycin Induces the G0 Program of Transcriptional Repression in Yeast by Interfering with the TOR Signaling Pathway

机译:雷帕霉素通过干扰TOR信号转导途径诱导酵母转录抑制的G0程序

获取原文
           

摘要

The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway. Growth arrest of budding yeast cells treated with rapamycin is followed by the program of molecular events that characterizes entry into G0 (stationary phase), including the induction of polymerase (Pol) II genes typically expressed only in G0. Normally, progression into G0 is characterized by transcriptional repression of the Pol I and III genes. Here, we show that rapamycin treatment also causes the transcriptional repression of Pol I and III genes. The down-regulation of Pol III transcription is TOR dependent. While it coincides with translational repression by rapamycin, transcriptional repression is due in part to a translation-independent effect that is evident in extracts from a conditional tor2 mutant. Biochemical experiments reveal that RNA Pol III and probably transcription initiation factor TFIIIB are targets of repression by rapamycin. In view of previous evidence that TFIIIB and Pol III are inhibited when protein phosphatase 2A (PP2A) function is impaired, and that PP2A is a component of the TOR pathway, our results suggest that TOR signaling regulates Pol I and Pol III transcription in response to nutrient growth signals.
机译:大环内酯类抗生素雷帕霉素通过干扰高度保守的TOR(雷帕霉素的靶标)信号传导途径来抑制细胞增殖。用雷帕霉素处理的出芽酵母细胞的生长停滞之后是表征进入G 0 (静止期)的分子事件程序,包括诱导通常仅在G中表达的聚合酶(Pol)II基因 0 。通常,进展为G 0 的特征在于Pol I和III基因的转录抑制。在这里,我们显示雷帕霉素治疗还引起Pol I和III基因的转录抑制。 Pol III转录的下调与TOR有关。虽然它与雷帕霉素的翻译抑制相吻合,但转录抑制部分归因于翻译非依赖性作用,这在条件 tor2 突变体的提取物中很明显。生化实验表明,RNA Pol III和可能的转录起始因子TFIIIB是雷帕霉素抑制的靶标。鉴于以前的证据表明,当蛋白磷酸酶2A(PP2A)功能受损时TFIIIB和Pol III会被抑制,并且PP2A是TOR途径的组成部分,我们的结果表明TOR信号传导响应于营养增长信号。

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