REL NF-KAPPA-B TRANSCRIPTION FACTORS AND I-KAPPA-B INHIBITORS - EVOLUTION FROM A UNIQUE COMMON ANCESTOR/

From the sequences of Rel/NF-kappa B and I kappa B proteins, we constr ucted an alignment of their Rel Homology Domain (RHD) and ankyrin repe at domain, Using this alignment, we performed tree reconstruction with both distance matrix and parsimony analysis and estimated the branchi ng robustness using bootstrap resampling methods, We defined four subf amilies of Rel/NF-kappa B transcription factors: (i) cRel, RelA, ReLB, Dorsal and Dif; (ii) NF-kappa B1 and NF-kappa B2; (iii) Relish and (i v) NF-AT factors, the most divergent members, Subfamilies I and II are clustered together whereas Relish diverged earlier than other Rel/NF- kappa B proteins, Three subfamilies of I kappa B inhibitors were also defined: (i) NF-kappa B1 and NF-kappa B2; (ii) close to subfamily I, t he short I kappa B proteins I kappa B alpha. I kappa B beta and Bcl-3; (iii) Relish that diverged earlier than other I kappa B inhibitors, O ur definition of groups and subfamilies fits to structural and functio nal features of the Rel/NF-kappa B and I kappa B proteins, We also sho wed that ankyrin repeats of NF-kappa B1, NF-kappa B2 and Relish are sh ort I kappa B-specific ankyrin motifs. These proteins defining a link between Rel/NF-kappa B and I kappa B families, we propose that all the se factors evolved from a common ancestral RHD-ankyrin structure withi n a unique superfamily, explaining the specificities of interaction be tween the different Rel/NF-kappa B dimers and the various I kappa B in hibitors.