• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >FAST Is a Survival Protein That Senses Mitochondrial Stress and Modulates TIA-1-Regulated Changes in Protein Expression
【24h】

FAST Is a Survival Protein That Senses Mitochondrial Stress and Modulates TIA-1-Regulated Changes in Protein Expression

机译：FAST是一种存活蛋白，可感知线粒体应激并调节TIA-1调控的蛋白表达变化

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

摘要

The Fas-activated serine/threonine phosphoprotein (FAST) is tethered to the outer mitochondrial membrane, where it interacts with BCL-XL (17). Here we show that RNA interference-mediated knockdown of endogenous FAST results in apoptosis, whereas overexpressed recombinant FAST inhibits Fas- and UV-induced apoptosis, indicating that FAST is a survival protein. The antiapoptotic effects of FAST are regulated by interactions with the translational silencer TIA-1: a FAST mutant lacking its TIA-1-binding domain does not inhibit apoptosis, and overexpressed recombinant TIA-1 inhibits the antiapoptotic effects of FAST. Because the antiapoptotic effects of FAST require ongoing protein synthesis, we hypothesized that FAST might function by preventing TIA-1-mediated silencing of mRNAs encoding inhibitors of apoptosis. Consistent with this hypothesis, FAST promotes the expression of cotransfected reporter proteins, a process that requires its TIA-1-binding domain and is inhibited by overexpressed recombinant TIA-1. More compellingly, recombinant FAST increases the expression of endogenous cIAP-1 and XIAP, but not GAPDH, in transfected HeLa cells. Because FAST is released from mitochondria in cells undergoing Fas- or UV-induced apoptosis, we propose that FAST serves as a sensor of mitochondrial stress that modulates a TIA-1-regulated posttranscriptional stress response program.
机译：Fas激活的丝氨酸/苏氨酸磷酸蛋白（FAST）被束缚在线粒体外膜上，并与BCL-X L 相互作用（17）。在这里我们显示内源性FAST的RNA干扰介导的敲低导致凋亡，而过度表达的重组FAST抑制Fas和UV诱导的凋亡，表明FAST是一种存活蛋白。 FAST的抗凋亡作用是通过与翻译沉默子TIA-1的相互作用来调节的：缺少其TIA-1结合域的FAST突变体不会抑制细胞凋亡，而过表达的重组TIA-1则抑制FAST的抗凋亡作用。因为FAST的抗凋亡作用需要正在进行的蛋白质合成，所以我们假设FAST可能通过阻止TIA-1介导的编码凋亡抑制剂的mRNA沉默而起作用。与该假设一致，FAST促进了共转染的报道蛋白的表达，该过程需要其TIA-1结合域并被过表达的重组TIA-1抑制。更令人信服的是，重组FAST增加了转染的HeLa细胞中内源性cIAP-1和XIAP的表达，但没有增加GAPDH的表达。因为FAST是在经历Fas或UV诱导的细胞凋亡的细胞中从线粒体释放的，所以我们建议FAST充当线粒体应激的传感器，调节TIA-1调控的转录后应激反应程序。

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