...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Specific isoforms of p73 control the induction of cell death induced by the viral proteins, E1A or apoptin.
【24h】

Specific isoforms of p73 control the induction of cell death induced by the viral proteins, E1A or apoptin.

机译：p73的特定同工型控制由病毒蛋白，E1A或凋亡蛋白诱导的细胞死亡诱导。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A member of the p53 family, p73, has several isoforms and differentially regulates transcription of genes involved in the control of the cell cycle and apoptosis. We have previously shown efficient and p53-independent, tumor-specific cell death induced by the viral proteins E1A and Apoptin. Here, we demonstrate that the induction of apoptosis by these viral proteins involves activation of TAp73. Both E1A and Apoptin induced expression of endogenous TAp73 and the p53/p73 BH3-only pro-apoptotic target, PUMA, independently of the p53 function. Furthermore, exogenous expression of TAp73 isoforms, particularly TAp73beta, sensitized cells to killing by both E1A and Apoptin, while expression of DeltaNp73alpha blocked this activity. Besides, knockout of the p73 regulator, c-Abl, attenuated E1A-induced apoptosis. In accordance with the role of p73 in apoptosis induced by these viral proteins, overexpression of TAp73beta strongly induced apoptosis in p53-deficient cancer cells in vitro and in HNSCC xenografts. Using a doxycycline-inducible system, we provide evidence for target selectivity and significant differences in protein stability for specific p73 isoforms, suggesting a diverse and pivotal role for p73 in response to various genotoxic agents. Collectively, our data show that in the absence of the p53 function, viral proteins E1A and Apoptin utilize the p73 pathway to induce efficient tumor cell death.
机译：p53家族的成员p73具有几种同工型，并差异调节与细胞周期和细胞凋亡控制有关的基因的转录。我们之前已经显示了由病毒蛋白E1A和Apoptin诱导的有效且不依赖p53的肿瘤特异性细胞死亡。在这里，我们证明这些病毒蛋白诱导的细胞凋亡涉及激活TAp73。 E1A和Apoptin均可诱导内源性TAp73和仅p53 / p73 BH3促凋亡靶标PUMA的表达，而与p53功能无关。此外，TAp73亚型，特别是TAp73beta的外源表达使细胞易于被E1A和Apoptin杀死，而DeltaNp73alpha的表达则阻止了该活性。此外，敲除p73调节剂c-Abl可减弱E1A诱导的细胞凋亡。根据p73在这些病毒蛋白诱导的凋亡中的作用，TAp73beta的过表达在体外和HNSCC异种移植物中强烈诱导了p53缺陷型癌细胞的凋亡。使用强力霉素诱导系统，我们提供了针对特定p73亚型的靶标选择性和蛋白质稳定性的显着差异的证据，表明p73对多种遗传毒性剂的响应具有多种多样且至关重要的作用。总体而言，我们的数据表明，在缺乏p53功能的情况下，病毒蛋白E1A和Apoptin利用p73途径诱导有效的肿瘤细胞死亡。

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