HIF-1通过分泌的神经元氨酶对抗p53-介导的亡
Ataman Sendoel1, Ines Kohler, Christof Fellmann
1Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Nature
|June 4, 2010
概括
低氧诱导因子 (HIF) 通过调节TYR-2来防止DNA损伤诱导的细胞死亡. 这种保存机制表明HIF如何从远处影响细胞亡,影响癌症的进展.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 缺氧诱导因子 (HIF) 调节细胞对氧气水平的反应.
- 在瘤中增加的HIFalpha与预后不佳相关.
- 癌症中HIF和亡之间的关系还不清楚.
研究的目的:
- 为了研究HIF在DNA损伤诱导的亡中的作用.
- 阐明HIF影响计划细胞死亡的分子机制.
主要方法:
- 使用Caenorhabditis elegans作为一个模型生物.
- 研究了HIF-1的功能及其与CEP-1 (p53同源) 的相互作用.
- 分析了TYR-2在ASJ感觉神经元中的作用及其人类同类TRP2/DCT在黑色素瘤细胞中的作用.
主要成果:
- 在C. elegans中,HIF-1对抗CEP-1以保护生殖细胞免受亡.
- 在ASJ神经元中TYR-2的升级调节调解了HIF-1的抗apoptotic功能.
- 人类黑色素瘤细胞中TRP2的抑制会增加细胞亡,这表明功能得到保护.
结论:
- HIF-1对DNA损伤诱导的亡起着保护作用.
- 一个涉及分泌的TYR-2的新型信号通路调解了HIF对细胞命运的远程控制.
- 这些发现揭示了缺氧和被编程细胞死亡之间的进化保存的联系.
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