...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular biology of the cell >Inhibition of the Ubiquitin-Proteasome System Induces Stress Granule Formation
【24h】

Inhibition of the Ubiquitin-Proteasome System Induces Stress Granule Formation

机译：泛素-蛋白酶体系统的抑制诱导应激颗粒形成。

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

摘要

The inhibition of the ubiquitin-dependent proteasome system (UPS) via specific drugs is one type of approach used to combat cancer. Although it has been suggested that UPS inhibition prevents the rapid decay of AU-rich element (ARE)-containing messages, very little is known about the cellular mechanisms leading to this effect. Here we establish a link between the inhibition of UPS activity, the formation of cytoplasmic stress granules (SGs), and mRNA metabolism. The assembly of the SGs requires the phosphorylation of the translation initiation factor eIF2α by a mechanism involving the stress kinase GCN2. On prolonged UPS inhibition and despite the maintenance of eIF2α phosphorylation, SGs disassemble and translation recovers in an Hsp72 protein-dependent manner. The formation of these SGs coincides with the disassembly of processing bodies (PBs), known as mRNA decay entities. As soon as the SGs assemble, they recruit ARE-containing messages such as p21cip1 mRNA, which are stabilized under these conditions. Hence, our findings suggest that SGs could be considered as one of the players that mediate the early response of the cell to proteasome inhibitors by interfering temporarily with mRNA decay pathways.
机译：通过特异性药物抑制泛素依赖性蛋白酶体系统（UPS）是用于抗击癌症的一种方法。尽管有人提出UPS抑制作用会阻止富含AU的元素（ARE）的信息迅速衰减，但导致这种效应的细胞机制知之甚少。在这里，我们建立了抑制UPS活动，细胞质应激颗粒（SGs​​）的形成和mRNA代谢之间的联系。 SG的组装需要通过涉及应激激酶GCN2的机制使翻译起始因子eIF2α磷酸化。在长时间的UPS抑制下，尽管eIF2α磷酸化得以维持，SGs仍会分解，并且翻译会以Hsp72蛋白依赖性方式恢复。这些SG的形成与称为mRNA衰变实体的加工体（PB）的分解相吻合。 SG组装完成后，就会募集包含ARE的信息，例如p21 cip1 mRNA，这些信息在这些条件下会稳定下来。因此，我们的发现表明，SGs可以被认为是通过暂时干扰mRNA衰变途径来介导细胞对蛋白酶体抑制剂早期反应的参与者之一。

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