Redox Regulation of Nuclear Post-Translational Modifications During NF-κB Activation

The transcription factor NF-kappa B controls the expression of hundreds of genes involved in the regulation of the immune/inflammatory response, development, and apoptosis. In resting cells, NF-kappa B proteins are sequestered in the cytoplasm through their tight association with I kappa B proteins. NF-kappa B activation relies on the signal-induced I kappa B phosphorylation and degradation, thereby allowing the nuclear translocation of NF-kappa B proteins. In the nucleus, several post-translational modifications of NF-kappa B and chromatin remodeling of target genes are mandatory for NF-kappa B DNA binding and full transcription. Since 1991, reactive oxygen species (ROS) have been implicated in NF-kappa B activation. ROS enhance the cytoplasmic signaling pathways leading to NF-kappa B nuclear translocation, but reduction/oxidation (redox) also controls several key steps in the nuclear phase of the NF-kappa B program, including chromatin remodeling, recruitment of co-activators, and DNA binding. Here we describe the redox regulation of NF-kappa B activity in the nucleus. Antioxid. Redox Signal. 11, 2209-2222.