DNA损伤
细胞生物学
下调和上调
支票1
先天免疫系统
生物
DNA修复
NKG2D公司
免疫系统
细胞周期检查点
癌症研究
细胞凋亡
DNA
细胞周期
免疫学
细胞毒性T细胞
遗传学
基因
体外
作者
Stephan Gasser,Sandra Oršulić,Eric J. Brown,David H. Raulet
出处
期刊:Nature
[Springer Nature]
日期:2005-07-03
卷期号:436 (7054): 1186-1190
被引量:1188
摘要
Some stimulatory receptors of the innate immune system, such as the NKG2D receptor (also called KLRK1) expressed by natural killer cells and activated CD8(+)T cells, recognize self-molecules that are upregulated in diseased cells by poorly understood mechanisms. Here we show that mouse and human NKG2D ligands are upregulated in non-tumour cell lines by genotoxic stress and stalled DNA replication, conditions known to activate a major DNA damage checkpoint pathway initiated by ATM (ataxia telangiectasia, mutated) or ATR (ATM- and Rad3-related) protein kinases. Ligand upregulation was prevented by pharmacological or genetic inhibition of ATR, ATM or Chk1 (a downstream transducer kinase in the pathway). Furthermore, constitutive ligand expression by a tumour cell line was inhibited by targeting short interfering RNA to ATM, suggesting that ligand expression in established tumour cells, which often harbour genomic irregularities, may be due to chronic activation of the DNA damage response pathway. Thus, the DNA damage response, previously shown to arrest the cell cycle and enhance DNA repair functions, or to trigger apoptosis, may also participate in alerting the immune system to the presence of potentially dangerous cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI