The DNA-dependent protein kinase participates in the activation of NFκB following DNA damage

The DNA-dependent protein kinase participates in the activation of NFκB following DNA damage
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DOI:
10.1006/bbrc.1998.8741
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发表时间:
1998-06-09
影响因子:
3.1
通讯作者:
Price, BD
Price, BD
中科院分区:
生物学4区
文献类型:
--
作者:
Basu, S;Rosenzweig, KR;Price, BD

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NFkB转录因子被多种刺激激活,包括电离辐射(IR)和细胞因子TNF α。研究了DNA-PK(一种参与DNA损伤应答的蛋白激酶)在IR和TNF α激活NF κ B B中的作用。在表达DNA-PK的M059 K细胞中,NF kappa B被TNF α和IR激活。在不表达DNA-PK的M059 J细胞中,IR没有激活NF kappa B,而仍然观察到TNF α对NF kappa B的诱导。在HeLa细胞中,一种DNA-PK抑制剂渥曼青霉素可阻断IR对NF κ B B的诱导,但不能阻断TNF α对NF κ B的诱导。DNA-PK还在体外磷酸化NF κ B B抑制蛋白IkB-α和IkB-β,缺失分析表明DNA-PK磷酸化IkB-β的两个不同区域。这些结果表明DNA-PK参与IR而不是TNF α激活NF κ B B。(C)北京:科学出版社.
The NFkB transcription factor is activated by diverse stimuli, including Ionizing Radiation (IR) and the cytokine TNF alpha. The role of DNA-PK, a protein kinase involved in the response to DNA damage, in the activation of NF kappa B by IR and TNF alpha was examined. In M059K cells, which express DNA-PK, NF kappa B was activated by both TNF alpha and IR. In M059J cells, which do not express DNA-PK, IR did not activate NF kappa B, whereas TNF alpha induction of NF kappa B was still observed. In HeLa cells, wortmannin, an inhibitor of DNA-PK, blocked the induction of NF kappa B by IR but not by TNF alpha. DNA-PK also phosphorylated the NF kappa B inhibitory proteins IkB-alpha and IkB-beta in vitro, and deletion analysis demonstrated that DNA-PK phosphorylates 2 distinct regions of IkB-beta, These results indicate that DNA-PK participates in the activation of NF kappa B by IR but not by TNF alpha. (C) 1998 Academic Press.