Understanding the logic of IκB:NF-κB regulation in structural terms

NF-κB is an inducible transcription factor that controls expression of diverse stress response genes. The entire mammalian NF-κB family is generated from a small cadre of five gene products that assemble with one another in various combinations to form active homo- and heterodimers. The ability of NF-κB to alter target gene expression is regulated at many levels. Chief among these regulatory mechanisms is the noncovalent association in the cell cytoplasm of NF-κB dimers with IκB inhibitor proteins. Removal of IκB leads to accumulation of active NF-κB within the cell nucleus where it binds to specific DNA sequences contained within the promoter regions of target genes and initiates recruitment of general transcription factors and assembly of the basal transcription machinery. Here we provide a detailed description of these fundamental NF-κB regulatory events using as a basis macromolecular structures and experimental data derived from structure-based biochemistry.