...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >RAD6 Regulates the Dosage of p53 by a Combination of Transcriptional and Posttranscriptional Mechanisms
【24h】

RAD6 Regulates the Dosage of p53 by a Combination of Transcriptional and Posttranscriptional Mechanisms

机译：RAD6通过转录和转录后机制的结合来调节p53的剂量。

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

摘要

Maintaining an appropriate cellular concentration of p53 is critical for cell survival and normal development in various organisms. In this study, we provide evidence that the human E2 ubiquitin-conjugating enzyme RAD6 plays a critical role in regulating p53 protein levels under both normal and stress conditions. Knockdown and overexpression of RAD6 affected p53 turnover and transcription. We showed that RAD6 can form a ternary complex with MDM2 and p53 that contributes to the degradation of p53. Chromatin immunoprecipitation (ChIP) analysis showed that RAD6 also binds to the promoter and coding regions of the p53 gene and modulates the levels of H3K4 and K79 methylation on local chromatin. When the cells were exposed to stress stimuli, the RAD6-MDM2-p53 ternary complex was disrupted; RAD6 was then recruited to the chromatin of the p53 gene, resulting in an increase in histone methylation and p53 transcription. Further studies showed that stress-induced p53 transcriptional activation, cell apoptosis, and disrupted cell cycle progression are all RAD6 dependent. Overall, this work demonstrates that RAD6 regulates p53 levels in a “yin-yang” manner through a combination of two distinct mechanisms in mammalian cells.
机译：维持适当的p53细胞浓度对于各种生物的细胞存活和正常发育至关重要。在这项研究中，我们提供的证据表明，人E2泛素结合酶RAD6在正常和应激条件下均在调节p53蛋白水平中起关键作用。敲除和过度表达RAD6影响p53营业额和转录。我们表明，RAD6可以与MDM2和p53形成三元复合物，从而导致p53的降解。染色质免疫沉淀（ChIP）分析表明，RAD6还与p53基因的启动子和编码区结合，并调节局部染色质上H3K4和K79甲基化的水平。当细胞受到应激刺激时，RAD6-MDM2-p53三元复合物被破坏。然后将RAD6募集到p53基因的染色质上，导致组蛋白甲基化和p53转录增加。进一步的研究表明，应激诱导的p53转录激活，细胞凋亡和破坏的细胞周期进程均取决于RAD6。总体而言，这项工作表明RAD6通过哺乳动物细胞中两种不同机制的组合以“阴阳”方式调节p53水平。

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