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Review
. 2011 Jan;21(1):103-15.
doi: 10.1038/cr.2010.178. Epub 2010 Dec 28.

Crosstalk of reactive oxygen species and NF-κB signaling

Michael J Morgan  1 , Zheng-gang Liu
Affiliations
Review

Crosstalk of reactive oxygen species and NF-κB signaling

Michael J Morgan et al. Cell Res. 2011 Jan.

Abstract

NF-κB proteins are a family of transcription factors that are of central importance in inflammation and immunity. NF-κB also plays important roles in other processes, including development, cell growth and survival, and proliferation, and is involved in many pathological conditions. Reactive Oxygen Species (ROS) are created by a variety of cellular processes as part of cellular signaling events. While certain NF-κB-regulated genes play a major role in regulating the amount of ROS in the cell, ROS have various inhibitory or stimulatory roles in NF-κB signaling. Here we review the regulation of ROS levels by NF-κB _targets and various ways in which ROS have been proposed to impact NF-κB signaling pathways.

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Figures

Figure 1
Figure 1
Intracellular Sources of ROS. The mitochondria are a major source of ROS, especially through electron leakage from Complexes I and III. ROS are also produced by NAD(P)H oxidases, sometimes in response to cytokines and other growth factor receptors, which may also utilize other pathways to produce ROS for use in their signaling pathways. Lastly, metabolic enzymes often create ROS as side products or through nonspecific reactions.
Figure 2
Figure 2
Activation of NF-κB and regulation of downstream transcriptional antioxidant and pro-oxidant _targets. NF-κB is activated primarily by two pathways: the canonical pathway (shown on left) and the noncanonical pathway (shown on right). Downstream binding of the NF-κB proteins to DNA regulates downstream transcriptional _targets. Shown are many potential antioxidant and pro-oxidant _targets that have been proposed in the literature.
Figure 3
Figure 3
Crosstalk of ROS with NF-κB signaling pathways. ROS interacts with NF-κB at various places within the signaling pathway. Many of these interactions occur in a cell type-specific manner. ROS has been proposed to both activate and inactivate the IKK complex leading to an effect on the downstream _targets. Often ROS has been shown to activate NF-κB through alternative IκBα phosphorylation, which may or may not result in the degradation of IκBα. Lastly, ROS may influence the DNA binding properties of the NF-κB proteins themselves. Oxidation of p50 on its DNA binding domain has been shown to prevent its DNA binding, and must be reversed in the nucleus by a Trx1-dependent process involving Ref-1. On the other hand, the phosphorylation of RelA that is influenced by ROS-dependent processes leads to greater NF-κB activation.
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