NF‐κB regulation: the nuclear response

•  Introduction •  Activation of NF‐ κ B •  Regulators of NF‐ κ B activation •  Nuclear regulation of NF‐κB ‐  B cell lymphoma 3 (Bcl‐3) ‐  I κB‐ζ ‐  UXT, ZAS3 and PDLIM2•  Post‐translational modification of NF‐ κ B complex in the nucleus ‐  Phosphorylation ‐  Acetylation and Deacetylation ‐  Sumoylation•  Nuclear regulators of NF‐κB: potential molecular chaperones •  ConclusionAbstract 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 I κ B‐ 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.