NF-κB regulation: the nuclear response

Nuclear factor κB (NF-κB) is an inducible transcription factor that tightly regulates the expression of a large cohort of genes. As a key component of the cellular machinery NF-κB is involved in a wide range of biological processes including innate and adaptive immunity, inflammation, cellular stress responses, cell adhesion, apoptosis and proliferation. Appropriate regulation of NF-κB is critical for the proper function and survival of the cell. Aberrant NF-κB activity has now been implicated in the pathogenesis of several diseases ranging from inflammatory bowel disease to autoimmune conditions such as rheumatoid arthritis. Systems governing NF-κB activity are complex and there is an increased understanding of the importance of nuclear events in regulating NF-κB's activities as a transcription factor. A number of novel nuclear regulators of NF-κB such as IκB-ζ and PDZ and LIM domain 2 (PDLIM2) have now been identified, adding another layer to the mechanics of NF-κB regulation. Further insight into the functions of these molecules raises the prospect for better understanding and rational design of therapeutics for several important diseases.