The NF-kappaB family of transcription factors and its regulation.

Abstract

Nuclear factor-kappaB (NF-kappaB) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappaB activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappaB proteins (IkappaBs), which retain inactive NF-kappaB dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappaB activation converge on the IkappaB kinase (IKK) complex, which is responsible for IkappaB phosphorylation and is essential for signal transduction to NF-kappaB. Additional regulation of NF-kappaB activity is achieved through various post-translational modifications of the core components of the NF-kappaB signaling pathways. In addition to cytosolic modifications of IKK and IkappaB 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-kappaB response. This has made the NF-kappaB pathway a paradigm for understanding general principles of signal transduction and gene regulation.