Redox regulation of NF-κB activation: Distinct redox regulation between the cytoplasm and the nucleus

Reduction/oxidation (redox) regulation mediates numerous cellular responses and contributes to several physiological diseases. The transcription factor nuclear factor κB (NF-κB) is known to be a redox-sensitive factor. NF-κB plays a central role in immune responses and inflammation, through regulation of the gene expression of a large number of cytokines and other immune response genes. NF-κB is trapped in the cytoplasm in stimulated cells and translocates into the nucleus in response to several stimuli, including oxidative stress. Reactive oxygen species enhance the signal transduction pathways for NF-κB activation in the cytoplasm and translocation into the nucleus. In contrast, the DNA binding activity of oxidized NF-κB is significantly diminished, and that activity is restored by reducing enzymes, such as thioredoxin or redox factor 1. This review describes the signal transduction pathways for NF-κB activation and redox regulation of NF-kB activation in the cytoplasm and nucleus.