NF-κB, an Evolutionarily Conserved Mediator of Immune and Inflammatory Responses

  • Changchun Xiao
  • Sankar Ghosh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 560)


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.


Ankyrin Repeat Toll Pathway Toll Receptor Necrosis Factor Receptor Associate Factor Conserve Transcription Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Changchun Xiao
    • 1
  • Sankar Ghosh
    • 1
  1. 1.Section of Immunobiology, Department of Molecular Biophysics and BiochemistryYale University School of MedicineNew Haven

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