The NF-κB Family of Transcription Factors and Its Regulation
- 1Department of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520
- 2Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York 10032
- Correspondence: sg2715{at}columbia.edu
Abstract
Nuclear factor-κB (NF-κB) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-κB activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-κB proteins (IκBs), which retain inactive NF-κB dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-κB activation converge on the IκB kinase (IKK) complex, which is responsible for IκB phosphorylation and is essential for signal transduction to NF-κB. Additional regulation of NF-κB activity is achieved through various post-translational modifications of the core components of the NF-κB signaling pathways. In addition to cytosolic modifications of IKK and IκB 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-κB response. This has made the NF-κB pathway a paradigm for understanding general principles of signal transduction and gene regulation.
Footnotes
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Editors: Louis M. Staudt and Michael Karin
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Additional Perspectives on NF-κB available at www.cshperspectives.org
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