NF-κB regulation: lessons from structures

The signaling module that specifies nuclear factor-?? (NF-?B) activation is a three-component system: NF-?B, inhibitor of NF-?? (I??), and I?? kinase complex (IKK). IKK receives upstream signals from the surface or inside the cell and converts itself into a catalytically active form, leading to the destruction of I?B in the inhibited I?B:NF-?B complex, leaving active NF-?B free to regulate target genes. Hidden within this simple module are family members that all can undergo various modifications resulting in expansion of functional spectrum. Three-dimensional structures representing all three components are now available. These structures have allowed us to interpret cellular observations in molecular terms and at the same time helped us to bring forward new concepts focused towards understanding the specificity in the NF-?B activation pathway.