NF-κB, an Evolutionarily Conserved Mediator of Immune and Inflammatory Responses
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NF-κB is a family of structurally related and evolutionarily conserved transcription factors. There are five NF-κB proteins in mammals: RelAIp65, RelB, c-Rel, NF-κB1 (p50 and its precursor p105), and NF-κB2 (p52 and its precursor p100); and three in flies: Dorsal, Dif, and Relish. All NFκB proteins contain a N-terminal 300 amino acid re1 homology domain, which is responsible for DNA binding, dimerization, and interaction with the inhibitors of NF-κB, the IκB family proteins. RelA, RelB, c-Rel, Dorsal, and Dif have a transcription activation domain at their C-termini, where p100, p105, and Relish contain ankyrin repeats, signature structures of IκB proteins. NF-κB proteins form hetero- or homodimers and are retained in the cytoplasm by IκBs. There are five IκB proteins in mammals: IκBα, IκBβ, IκBγ, IκBε, and Bcl-3; and one IκB protein in fly: Cactus. 1κBα and IκBβ share a tripartite organization: an N-terminal domain that is phosphorylated in response to signals, a central ankyrin repeat domain, and a C-terminal PEST domain that is involved in the basal turnover of the protein. All other IκB proteins have central ankyrin repeat domain, but differ from IκBα and IκBβ at their N- and C- terminal domains. IκB proteins form complexes with NF-κB dimers, with ankyrin repeats in direct contact with re1 homology domains. This interaction is essential to keep NF-κB dimers in the cytoplasm, thus physically sequestrating them from their transcriptional target.
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- NF-κB, an Evolutionarily Conserved Mediator of Immune and Inflammatory Responses
- Book Title
- Mechanisms of Lymphocyte Activation and Immune Regulation X
- Book Subtitle
- Innate Immunity
- pp 41-45
- Print ISBN
- Online ISBN
- Series Title
- Advances in Experimental Medicine and Biology
- Series Volume
- Series ISSN
- Springer US
- Copyright Holder
- Springer Science + Business Media, Inc.
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- Editor Affiliations
- 6. University of California Irvine
- 7. NIAID, NIH
- 8. Rockefeller University
- Author Affiliations
- 9. Section of Immunobiology, Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connectient, 06520
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