Signal Transduction Pathways in Development and Immunity: NFκB/Rel Pathways


The nuclear factor kappa B (NFκB)/Rel signal transduction pathway is conserved from simple multicellular eukaryotes, such as sponges and insects, to humans and controls a variety of processes involved primarily in immunity and development. The NFκB family of transcription factors includes several structurally related proteins that form dimers, which regulate the expression of numerous genes by binding to specific deoxyribonucleic acid (DNA) sites near these genes. In mammals, the NFκB pathway is important in the control of innate and adaptive immunity, immune cell development, cell proliferation and cell survival. In insects, the NFκB pathway controls the establishment of dorsal–ventral polarity in the early embryo and an antimicrobial response. Activation of NFκB transcription factors occurs via a series of biochemical steps and involves translocation of NFκB from the cytoplasm to the nucleus where it can activate gene expression. Misregulation of the NFκB pathway is also implicated in several human disease states, including many types of cancer and inflammatory diseases.

Key concepts:

  • NFκB and Rel proteins are part of a family of transcription factors whose activity is controlled primarily by subcellular localization.

  • Many extracellular signals can activate a multicomponent signal transduction pathway that leads to nuclear localization of NFκB/Rel proteins where they control the transcription of many important effector genes.

  • NFκB/Rel transcription factors control a number of evolutionarily conserved developmental and immune processes.

  • In Drosophila, NFκB/Rel signalling controls the immune response of flies to fungal and bacterial infections.

  • In vertebrates, NFκB/Rel signalling controls the innate immune response, cell survival and the development of several specific cell types, such as liver cells, immune cells and skin cells.

  • Misregulation of NFκB/Rel activity occurs in a number of human diseases, including several chronic inflammatory diseases and cancers.

Keywords: NF‐kappaB; Rel; Dorsal; transcription factor; immune response

Figure 1.

Generalized structures of the two classes of NFκB proteins. The Rel homology (RH) domain contains sequences important for DNA binding, inhibitor (IκB) binding, dimerization and nuclear localization (N). The C‐terminal halves contain inhibitory ankyrin repeats (the ‘NFκB’ proteins, top) or transactivation sequences (the ‘Rel’ proteins bottom). The top class of NFκB proteins can undergo proteolysis at the indicated region to remove the ankyrin repeat domain and generate an active DNA‐binding protein. See text for more details.

Figure 2.

Comparison of the NFκB signalling pathways in Drosophila and mammals. Shown at the right is the general scheme for activation of the NFκB signalling pathway. Shown at the left and centre are the corresponding components of the various NFκB pathways in Drosophila and mammals. See text for more details.



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Hayden MS, West AP and Ghosh S (2006) NF‐κB and the immune response. Oncogene 25: 6758–6780.

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Gilmore, Thomas D, and Tony Ip, Y(Sep 2009) Signal Transduction Pathways in Development and Immunity: NFκB/Rel Pathways. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002332.pub3]