Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB.
Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB.
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发表时间：
2000
影响因子：
7.4
通讯作者：
Y. Janssen-Heininger;M. Poynter;P. Baeuerle
中科院分区：
文献类型：
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作者：
Y. Janssen-Heininger;M. Poynter;P. Baeuerle
转录因子核因子-kappaB (NF-kappaB) 由于其在免疫和炎症基因、细胞凋亡和细胞增殖调节中的突出作用而受到广泛研究。十多年来，人们都知道 NF-kappaB 是一种氧化还原敏感的转录因子。由于许多相互矛盾的报道，氧化还原调节的贡献以及 NF-κB 激活途径中潜在氧化还原敏感位点的位置引起了激烈的争论。本杂志广泛讨论了 NF-kappaB 的氧化还原调节，读者可以参考关于该主题的两篇综合评论 [1,2]。随着抑制剂 IkappaB 降解附近信号中间体的识别，潜在的氧化还原敏感位点的数量正在迅速增加。本综述的目的是阐述对 TNF-α 和 IL-1β 等促炎细胞因子触发的 NF-kappaB 信号级联的最新见解。此外，还将回顾一氧化氮 (.NO) 在 NF-κB 调节中的作用。将讨论 IkappaB-α 降解上游发生的氧化还原调节的机会，以及氧化还原控制 NF-kappaB 亚基磷酸化的潜力。氧化还原敏感步骤可能取决于 NF-kappaB 激活剂的性质、所涉及的活性氧或氮物种的类型、激活的信号通路的选择性以及所研究的细胞类型。最后，讨论了 NF-κB 激活的氧化还原调节如何可能涉及多个亚细胞区室。
The transcription factor, nuclear factor-kappaB (NF-kappaB) has been studied extensively due to its prominent role in the regulation of immune and inflammatory genes, apoptosis, and cell proliferation. It has been known for more that a decade that NF-kappaB is a redox-sensitive transcription factor. The contribution of redox regulation and the location of potential redox-sensitive sites within the NF-kappaB activation pathway are subject to intense debate due to many conflicting reports. Redox regulation of NF-kappaB has been extensively addressed in this journal and the reader is referred to two comprehensive reviews on the subject [1,2]. With the identification of signaling intermediates proximal to the degradation of the inhibitor, IkappaB, the number of potential redox-sensitive sites is rapidly increasing. The purpose of this review is to address recent insights into the NF-kappaB signaling cascades that are triggered by proinflammatory cytokines such as TNF-alpha and IL-1beta. In addition, the role of nitrogen monoxide (.NO) in the regulation of NF-kappaB will be reviewed. Opportunities for redox regulation that occur upstream of IkappaB-alpha degradation, as well as the potential for redox control of phosphorylation of NF-kappaB subunits, will be discussed. Redox-sensitive steps are likely to depend on the nature of the NF-kappaB activator, the type of reactive oxygen or nitrogen species involved, the selectivity of signaling pathways activated, as well as the cell type under investigation. Lastly, it is discussed how redox regulation of NF-kappaB activation is likely to involve multiple subcellular compartments.