...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
【24h】

Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells

机译：响应紫外线响应P19ink4d的诱导改善了DNA修复并赋予神经母细胞瘤细胞中凋亡的抗性

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

摘要

The genetic instability driving tumorigenesis is fuelled by DNA damage and by errors made by the DNA replication. Upon DNA damage the cell organizes an integrated response not only by the classical DNA repair mechanisms but also involving mechanisms of replication, transcription, chromatin structure dynamics, cell cycle progression, and apoptosis. In the present study, we investigated the role of p19INK4d in the response driven by neuroblastoma cells against DNA injury caused by UV irradiation. We show that p19INK4d is the only INK4 protein whose expression is induced by UV light in neuroblastoma cells. Furthermore, p19INK4d translocation from cytoplasm to nucleus is observed after UV irradiation. Ectopic expression of p19INK4d clearly reduces the UV-induced apoptosis as well as enhances the cellular ability to repair the damaged DNA. It is clearly shown that DNA repair is the main target of p19INK4d effect and that diminished apoptosis is a downstream event. Importantly, experiments performed with CDK4 mutants suggest that these p19INK4d effects would be independent of its role as a cell cycle checkpoint gene. The results presented herein uncover a new role of p19INK4d as regulator of DNA-damage-induced apoptosis and suggest that it protects cells from undergoing apoptosis by allowing a more efficient DNA repair. We propose that, in addition to its role as cell cycle inhibitor, p19INK4d is involved in maintenance of DNA integrity and, therefore, would contribute to cancer prevention.
机译：通过DNA损伤和DNA复制所制备的误差，促进肿瘤的遗传不稳定性。在DNA损伤后，该细胞不仅通过经典DNA修复机制组织综合反应，还涉及复制，转录，染色质结构动力学，细胞周期进展和凋亡的机制。在本研究中，我们研究了p19ink4d在神经母细胞瘤细胞驱动的响应中的作用免受UV辐射引起的DNA损伤的响应。我们表明p19ink4d是唯一的墨水4蛋白，其表达在神经母细胞瘤细胞中由UV光引起。此外，在紫外线照射后观察到从细胞质与核的p19kin 4D易位。 P19ink4D的异位表达明显降低了紫外线诱导的细胞凋亡，并提高了修复受损DNA的细胞能力。清楚地表明，DNA修复是P19ink4D效应的主要目标，并且细胞凋亡的减少是下游事件。重要的是，用CDK4突变体进行的实验表明，这些p19ink4D效应与其作为细胞周期检查点基因的作用无关。此处展示的结果将P19ink4D作为DNA损伤诱导的细胞凋亡的调节剂揭开了新的作用，并表明它通过允许更有效的DNA修复来保护细胞经历细胞凋亡。我们提出，除了其作为细胞周期抑制剂的作用外，P19ink4D也参与维持DNA完整性，因此将有助于预防癌症。

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