...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >The contribution of p53 in the dynamics of cell cycle response to DNA damage interpreted by a mathematical model.
【24h】

The contribution of p53 in the dynamics of cell cycle response to DNA damage interpreted by a mathematical model.

机译：p53在细胞周期对DNA损伤的反应动力学中的作用由数学模型解释。

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

Despite numerous studies on the tumor suppressor p53, a complete picture of its role in cell arrest and killing in G(1), S and G(2)M phases after drug treatment is lacking. We tackled the analysis of the complexity of cell cycle effects combining the time-course measures with different techniques with the aid of a computer program simulating cell cycle progression. This mixed experimental-simulation approach enabled us to decode the dynamics of the cytostatic and cytotoxic responses to cisplatin and doxorubicin treatments in a p53--proficient colon carcinoma cell line (HCT-116) and in its p53-deficient counterpart. We achieved a separate evaluation of the activity of each cell cycle control and we connected these results with measures of p53 level in G(1), S and G(2)M. We confirmed the action of p53 in all cell cycle phases, but also the presence of strong p53-independent cytostatic and cytotoxic activities exerted by both drugs. In G(1) phase, p53 was responsible for a medium/long term block, distinctfrom the short-term block, which was p53-independent. The delay in traversing S phase was reduced by the presence of p53. In G(2)M phase, despite a strong p53-independent block, there was a weaker but more persistent p53-dependent block. At cytotoxic concentrations, p53-dependent and p53-independent cell death was observed. The former was poorly phase-specific, occurred earlier and exploited the apoptotic mechanism more than p53-independent death. Computer simulation produced a framework where previous partial and sometimes apparently contradictory observations of the p53-mediated effects could be reconciled and explained.
机译：尽管对肿瘤抑制因子p53进行了大量研究，但缺乏药物治疗后其在G（1），S和G（2）M期细胞停滞和杀死中的作用的完整图片。我们通过计算机程序模拟细胞周期进程，结合了时程测量和不同技术，对细胞周期效应的复杂性进行了分析。这种混合的实验模拟方法使我们能够解码p53缺陷结肠癌细胞系（HCT-116）和p53缺陷对应细胞对顺铂和阿霉素治疗的细胞生长抑制作用和细胞毒性反应的动力学。我们对每个细胞周期控制的活动进行了单独的评估，并将这些结果与G（1），S和G（2）M中p53的水平联系起来。我们证实了p53在所有细胞周期阶段均起作用，而且证实了这两种药物均具有强烈的不依赖p53的细胞抑制和细胞毒性活性。在G（1）阶段，p53负责中/长期阻断，与短期阻断不同，后者是独立于p53的。 p53的存在减少了穿越S相的延迟。在G（2）M阶段，尽管有一个强烈的p53依赖性阻滞，但有一个较弱但更持久的p53依赖性阻滞。在细胞毒性浓度下，观察到p53依赖性和p53非依赖性细胞死亡。前者的阶段特异性差，发生得较早，并且比p53非依赖性死亡更能利用凋亡机制。计算机模拟产生了一个框架，在该框架中可以调和并解释先前对p53介导的效应的部分甚至有时是矛盾的观察结果。

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