The NF-κB Family of Transcription Factors and Its Regulation

Nuclear factor-kappa B (NF-kappa B) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappa B activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappa B proteins (I kappa Bs), which retain inactive NF-kappa B dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappa B activation converge on the I kappa B kinase (IKK) complex, which is responsible for I kappa B phosphorylation and is essential for signal transduction to NF-kappa B. Additional regulation of NF-kappa B activity is achieved through various post-translational modifications of the core components of the NF-kappa B signaling pathways. In addition to cytosolic modifications of IKK and I kappa B proteins, as well as other pathway-specific mediators, the transcription factors are themselves extensively modified. Tremendous progress has been made over the last two decades in unraveling the elaborate regulatory networks that control the NF-kappa B response. This has made the NF-kappa B pathway a paradigm for understanding general principles of signal transduction and gene regulation.