...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Cross-talks in the p53 family: deltaNp63 is an anti-apoptotic target for deltaNp73alpha and p53 gain-of-function mutants.
【24h】

Cross-talks in the p53 family: deltaNp63 is an anti-apoptotic target for deltaNp73alpha and p53 gain-of-function mutants.

机译：p53家族的相声：deltaNp63是delNNp73alpha和p53功能获得性突变体的抗凋亡靶标。

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

The p53 family of transcription factors plays a pivotal role in the control of the cellular response to DNA damaging agents. In addition to pro-apoptotic molecules such as p53, TAp73 and TAp63, this gene family also encodes for the anti-apoptotic molecules deltaNp73, deltaNp63, deltaNp53, and p53 mutants are often found in tumor cells, that have the role to limit and to modulate the pro-apoptotic side of the family. The ratio between the different members of the family is critical to make the life or death decision following DNA damage and is tightly regulated by post-translational and transcriptional mechanisms. In this study we have uncovered a novel positive feedback that involves the transcriptional activation of the anti-apoptotic molecule deltaNp63 by the anti-apoptotic molecules deltaNp73 and mutant p53, and that is put into motion upon treatment with a subset of DNA damaging agents such as Doxorubicin and 5-FU. DeltaNp73 and mutant p53 associate with the deltaNp63 promoter inducing its transcription and this is enhanced by doxorubicin treatment. Furthermore we have observed that deltaNp73- and mutp53-mediated activation of the deltaNp63 promoter requires the functionality of the proximal CCAAT boxes of this promoter, being hampered by mutation of CCAAT boxes or by dominant negative NFYA expression. This mechanism may serve as an additional control of the response of a normal cell to DNA damage or as an anti-apoptotic barrier of cancer cells subjected to DNA damage.
机译：转录因子的p53家族在控制细胞对DNA损伤剂的反应中起着关键作用。除了促凋亡分子（例如p53，TAp73和TAp63）外，该基因家族还编码抗凋亡分子delNNp73，deltaNp63，deltaNp53和p53突变体，这些突变体通常在肿瘤细胞中发现，它们具有限制和抑制细胞凋亡的作用。调节家族中促凋亡的一面。家庭不同成员之间的比例对于DNA损伤后的生死决定至关重要，并且受翻译后和转录机制的严格调控。在这项研究中，我们发现了一种新颖的积极反馈，该反馈涉及抗凋亡分子delNNp73和突变体p53对抗凋亡分子delNNp63的转录激活，并且在用DNA破坏剂（例如阿霉素和5-FU。 DeltaNp73和突变体p53与deltaNp63启动子结合，诱导其转录，而阿霉素处理则增强了转录。此外，我们已经观察到，deltaNp73和mutp53介导的deltaNp63启动子的激活需要该启动子的近端CCAAT框的功能，而受CCAAT框的突变或显性负NFYA表达的阻碍。该机制可作为正常细胞对DNA损伤的反应的额外控制，或作为遭受DNA损伤的癌细胞的抗凋亡屏障。

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