Structure and Mechanism in NF- B/I B Signaling

In 1986, Sen and Baltimore (1986) identified a nuclearfactor specific for the immunoglobulin κ light-chain geneenhancer of B lymphocytes. Nearly a decade and a halflater, the transcription factor NF-κB is recognized for itsroles in such vital cellular processes as immune and inflammatory responses, cellular adhesion, growth and development, and apoptosis (Baeuerle and Henkel 1994;Baeuerle and Baltimore 1996; Baldwin 1996; Ghosh etal. 1998). Regulation of NF-κB activity is governed byseveral factors including selective dimer formation, sequence-specific DNA binding, and interactions with IκBinhibitor proteins. Most recently, the field of NF-κB biology has benefited from a series of timely and well-executed structural studies. X-ray crystallographic analysesof NF-κB, both alone and in complex with various DNAtargets, have resulted in the elucidation of rules that govern NF-κB dimerization and DNA-binding selectivity.Furthermore, the crystal structure of NF-κB in complexwith the IκBα inhibitor protein has provided a wealth ofinformation regarding the regulation of NF-κB activity.Here, we review these structures in the context of NF-κBsignaling and transcriptional activation...