通过NF-kappaB目标基因抑制JNK激活
G Tang1, Y Minemoto, B Dibling
1Ben May Institute for Cancer Research, Committee on Cancer Biology, University of Chicago, 5841 S. Maryland Avenue, MC 6027, Chicago, Illinois 60637, USA.
Nature
|November 20, 2001
概括
瘤亡因子-α (TNF-α) 信号涉及复杂的相互作用. 该IKK/NF-kappaB通路通过抑制JNK激活,部分通过XIAP,抑制TNF-α诱导的亡.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 免疫学 免疫学 免疫学
- 信号传输 信号传输
背景情况:
- 瘤亡因子-α (TNF-α) 是免疫反应,炎症和亡的关键调节者.
- 在暴露于TNF-α时,细胞命运的确定依赖于整合来自效应因子的信号,如IkappaB激酶 (IKK),c-Jun N-终端蛋白激酶 (JNK) 和caspases.
- 在TNF-α诱导的亡中,IKK/NF-kappaB和JNK通路之间的相互作用仍然不完全理解.
研究的目的:
- 为了研究IKK和JNK信号通路之间的交叉声响应TNF-alpha.
- 阐明这种交叉的作用调节TNF-α诱导的亡.
主要方法:
- 使用的小鼠胚胎纤维细胞缺乏IKKbeta或RelA/p65 (NF-kappaB亚单元).
- 分析了IKK/NF-kappaB通路调节对TNF-α介导的JNK激活的影响.
- 评估了X染色体链接的亡抑制剂 (XIAP) 在这种交叉中所做出的贡献.
主要成果:
- 该IKK/NF-kappaB通路负面调节TNF-α介导的JNK激活.
- 这种负交叉是部分由NF-kappaB诱导的XIAP调解的.
- 观察到的JNK激活的负调节是TNF-alpha信号的特异性,并不会影响IL-1的JNK激活.
结论:
- 该IKK/NF-kappaB通路积极抑制下游TNF-alpha的JNK激活.
- 这种涉及XIAP的抑制性交叉作用,有助于整体抑制TNF-α诱导的亡.
- 这些发现揭示了关键炎症信号通路之间的交叉调节的新机制.
相关概念视频
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02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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