A structural guide to proteins of the NF-kB signaling module

The prosurvival transcription factorNF-kB specifically binds promoterDNA to activate target gene expression. NF-kB is regulated through interactions with IkB inhibitor proteins. Active proteolysis of these IkB proteins is, in turn, under the control of the IkB kinase complex (IKK). Together, these three molecules form the NF-kB signaling module. Studies aimed at charac-terizing the molecular mechanisms of NF-kB, IkB, and IKK in terms of their three-dimen-sional structures have lead to a greater understanding of this vital transcription factor system. NF-kB is a master transcription factor thatresponds to diverse cell stimuli by activat-ing the expression of stress response genes. Multiple signals, including cytokines, growth factors, engagement of the T-cell receptor, and bacterial and viral products, induce NF-kB transcriptional activity (Hayden and Ghosh 2008). A point of convergence for the myriad of NF-kB inducing signals is the IkB kinase complex (IKK). Active IKK in turn control