Transcription Factor NF-κ B: Function, Structure, Regulation, Pathways, and Applications

NF-κB is a transcription factor found in most cells that plays a central role in the inflammatory, immunologic, apoptotic, and stress responses. NF-κB is a dimer composed of members of the Rel family of transcription factor subunits. It is normally sequestered in the cytoplasm by its inhibitor, IκB. Nearly all NF-κB-activating stimuli activate the IκB kinase, which phosphorylates IκB and thereby targets it for degradation. Newly freed NF-κB then enters the nucleus and mediates its various effects by activating its target genes. NF-κB activity is modulated by numerous mechanisms, including combinatorial specificity of its subunits and inhibitors, several forms of posttranslation modifications, and differences in signal transduction. NF-κB is of great therapeutic interest and we highlight its role in cancer and review modern drugs used to inhibit it. Finally, we discuss the role of NF-κB in learning, a hint that NF-κB has functions beyond those traditionally associated with it.