Rel/NF-κB transcription factors and IκB inhibitors: Evolution from a unique common ancestor

Abstract

From the sequences of Rel/NF-kB and IkB proteins, we constructed an alignment of their Rel Homology Domain (RHD) and ankyrin repeat domain. Using this alignment, we performed tree reconstruction with both distance matrix and parsimony analysis and estimated the branching robustness using bootstrap resampling methods. We de®ned four subfamilies of Rel/NF-kB transcription factors: (i) cRel, RelA, RelB, Dorsal and Dif; (ii) NF-kB1 and NF-kB2; (iii) Relish and (iv) NF-AT factors, the most divergent members. Subfamilies I and II are clustered together whereas Relish diverged earlier than other Rel/NF-kB proteins. Three subfamilies of IkB inhibitors were also de®ned: (i) NF-kB1 and NFkB2; (ii) close to subfamily I, the short IkB proteins IkBa, IkBb and Bcl-3; (iii) Relish that diverged earlier than other IkB inhibitors. Our de®nition of groups and subfamilies ®ts to structural and functional features of the Rel/NF-kB and IkB proteins. We also showed that ankyrin repeats of NF-kB1, NF-kB2 and Relish are short IkB-speci®c ankyrin motifs. These proteins de®ning a link between Rel/NF-kB and IkB families, we propose that all these factors evolved from a common ancestral RHD-ankyrin structure within a unique superfamily, explaining the speci®cities of interaction between the di erent Rel/NF-kB dimers and the various IkB inhibitors.

Hypoxia regulates iNOS expression in human normal peritoneal and adhesion fibroblasts through nuclear factor kappa B activation mechanism

“…The active DNA-binding forms are either homodimers (p65/p65) or heterodimers (p50/p65). In most cells, NF-κB is present within the cytoplasm as inactive complexes with inhibitory IκB-α protein (19)(20)(21). Activation of NF-κB in response to stimuli, such as hypoxia, cytokines, lipopolysaccharide (LPS), and oxidants involves activation of IκB kinase (IKK), phosphorylation, and proteolytic degradation of IκB-α, with a release of activated NF-κB.…”

Nuclear factor-kappa B pathways in Drosophila

“…All three proteins contain the well-conserved N-terminal Rel homology (RH) domain. Based on their protein structure rather then their sequence similarity, the NF-kB proteins have been subdivided into four subfamilies (Huguet et al, 1997). Dorsal and Dif belong to subfamily I, along with c-Rel, RelA and RelB.…”

“…The subfamily II and III proteins are activated by proteolysis that removes the ankyrin repeats, which are also present in IkB proteins. In contrast to vertebrates, Drosophila contains a single, independent IkB protein, called Cactus, which is most closely related to IkBa (Huguet et al, 1997).…”

Overexpression of a Novel XenopusRel mRNA Gene Induces Tumors in Early Embryos

“…[1][2][3][4][5][6][7]. The family includes the c-Rel oncoprotein, RelB, NF-B (both p65 or RelA, and p50 subunits), and the DORSAL patterning morphogen of Drosophila.…”