Transcriptional regulation via the NF-κB signaling module

Stimulus-induced nuclear factor-kappa B (NF-kappa B) activity, the central mediator of inflammatory responses and immune function, comprises a family of dimeric transcription factors that regulate diverse gene expression programs consisting of hundreds of genes. A family of inhibitor of kappa B (I kappa B) proteins controls NF-kappa B DNA-binding activity and nuclear localization. I kappa B protein metabolism is intricately regulated through stimulus-induced degradation and feedback re-synthesis, which allows for dynamic control of NF-kappa B activity. This network of interactions has been termed the NF-kappa B signaling module. Here, we summarize the current understanding of the molecular structures and biochemical mechanisms that determine NF-kappa B dimer formation and the signal-processing characteristics of the signaling module. We identify NF-kappa B-kappa B site interaction specificities and dynamic control of NF-kappa B activityas mechanisms that generate specificity in transcriptional regulation. We discuss examples of gene regulation that illustrate how these mechanisms may interface with other transcription regulators and promoter-associated events, and how these mechanisms suggest regulatory principles for NF-kappa B-mediated gene activation.