Transcriptional regulation via the NF-κB signaling module

Stimulus-induced nuclear factor- κ B (NF- κ 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 κ B (I κ B) proteins controls NF- κ B DNA-binding activity and nuclear localization. I κ B protein metabolism is intricately regulated through stimulus-induced degradation and feedback re-synthesis, which allows for dynamic control of NF- κ B activity. This network of interactions has been termed the NF- κ B signaling module. Here, we summarize the current understanding of the molecular structures and biochemical mechanisms that determine NF- κ B dimer formation and the signal-processing characteristics of the signaling module. We identify NF- κ B– κ B site interaction specificities and dynamic control of NF- κ B activity as 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- κ B-mediated gene activation.