The role of NF-κB in the regulation of cell stress responses

Nuclear factor-κB (NF-κB) is one of the key regulatory molecules in oxidative stress-induced cell activation. NF-κB is normally sequestered in the cytoplasm of nonstimulated cells and must translocate into the nucleus to regulate effector gene expression. A family of inhibitory proteins, IκBs, binds to NF-κB and masks its nuclear localization signal domain and therefore controls the translocation of NF-κB. Exposure of cells to extracellular stimuli that perturb redox balance results in rapid phosphorylation, ubiquitination, and proteolytic degradation of IκBs. This process frees NF-κB from the NF-κB/IκB complexes and enables NF-κB to translocate to the nucleus where it regulates gene transcription. Many effector genes including those encoding cytokines and adhesion molecules are in turn regulated by NF-κB. NF-κB is also an essential component of ionizing radiation (IR)-triggered signal transduction pathways that can lead to cell death or survival. The purpose of this review is to briefly summarize the recent progress in the studies of the role of reactive oxygen species (ROS), cytokines and ionizing radiation in NF-κB activation.