...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Nucleolar Sequestration of RelA (p65) Regulates NF-κB-Driven Transcription and Apoptosis
【24h】

Nucleolar Sequestration of RelA (p65) Regulates NF-κB-Driven Transcription and Apoptosis

机译：RelA（p65）的核仁隔离调节NF-κB驱动的转录和凋亡。

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

摘要

The molecular mechanisms that regulate nuclear NF-κB to determine whether the stimulation of this pathway has a pro- or antiapoptotic effect on cells have yet to be fully defined. Nuclear compartmentalization is increasingly recognized as an important mechanism for regulating the activity of transcription-related proteins and modulating cell growth and death. We have investigated whether such compartmentalization serves as a mechanism for regulating NF-κB transcriptional activity. We demonstrate that the RelA component of NF-κB is sequestered in the nucleolus in response to the proapoptotic NF-κB stimuli aspirin, serum withdrawal, and UV-C radiation. In contrast, RelA is excluded from the nucleolus in response to the cytokines tumor necrosis factor and TRAIL. We identify an N-terminal motif of RelA that is essential for the nucleolar localization of the protein and show that deleting this motif inhibits the translocation of RelA from the nucleoplasm to the nucleolus. We demonstrate that the nucleolar accumulation of RelA is paralleled by a decrease in basal levels of NF-κB transcriptional activity and by apoptosis. Furthermore, we show that the retention of RelA in the nucleoplasm inhibits this decrease in NF-κB-driven transcription and blocks apoptosis induced by aspirin and UV-C radiation. This work identifies a novel cellular mechanism for regulating NF-κB-driven transcription and apoptosis, involving the nucleolar sequestration of a key NF-κB subunit. These data contribute to the understanding of the complexities of NF-κB function and have considerable relevance to cancer prevention and therapy.
机译：调节核NF-κB以确定该途径的刺激是否对细胞具有促凋亡或抗凋亡作用的分子机制尚未完全确定。越来越多地认识到核区室化是调节转录相关蛋白活性并调节细胞生长和死亡的重要机制。我们已经研究了这种区室化是否充当调节NF-κB转录活性的机制。我们证明，NF-κB的RelA组分被隔离在核仁中，以响应促凋亡的NF-κB刺激物阿司匹林，血清戒断和UV-C辐射。相反，响应细胞因子肿瘤坏死因子和TRAIL，RelA从核仁中排除。我们鉴定了RelA的N末端基序，该基序对于蛋白质的核仁定位至关重要，并且表明删除该基序会抑制RelA从核质到核仁的转运。我们证明RelA的核仁积累与基础水平的NF-κB转录活性降低和细胞凋亡平行。此外，我们显示，RelA在核质中的保留抑制了NF-κB驱动的转录的这种降低，并阻止了阿司匹林和UV-C辐射诱导的凋亡。这项工作确定了一种新的调节NF-κB驱动的转录和凋亡的细胞机制，涉及关键NF-κB亚基的核仁隔离。这些数据有助于理解NF-κB功能的复杂性，并与癌症的预防和治疗具有重要的联系。

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