DNA损伤途径调节NKG2D受体的先天免疫系统连接体
Stephan Gasser1, Sandra Orsulic, Eric J Brown
1Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, California 94720-3200, USA.
Nature
|July 5, 2005
概括
DNA损伤反应途径上调疾病细胞上的NKG2D连接体. 这种机制提醒免疫系统,涉及ATM和ATR激酶,潜在的危险细胞.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 像NKG2D这样的先天性免疫受体通过未知的机制识别患病细胞上的自我分子.
- NKG2D在自然杀手细胞和激活的CD8 ((+) T细胞上表达.
研究的目的:
- 阐明NKG2D连接体在患病细胞中的上调调节机制.
- 为了研究DNA损伤反应途径在NKG2D连接体表达中的作用.
主要方法:
- 利用基因毒性压力并阻碍细胞系中的DNA复制.
- 使用药理和基因抑制ATR,ATM和Chk1激酶.
- 使用短干扰RNA准瘤细胞系中的ATM.
主要成果:
- 基因毒性压力和停滞的DNA复制在小鼠和人类非瘤细胞系中的NKG2D配体上调.
- 抑制ATR,ATM或Chk1可以防止连接体上调.
- 向ATM与siRNA减少了瘤细胞系中的构成性联结体表达.
结论:
- 由ATR和ATM启动的DNA损伤反应途径,可以对NKG2D连接体进行上调.
- 这种途径的慢性激活可能会驱动瘤细胞中的联结体表达.
- DNA损伤反应可能会提醒免疫系统注意危险的细胞.
相关概念视频
01:08Nucleotide Excision Repair
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01:08Nucleotide Excision Repair
Overview
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NF-κB-dependent Signaling Mechanism
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01:38Nucleotide Excision Repair
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01:28Cells of the Innate Immune Response
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