The Nfkb1 and Nfkb2 Proteins p105 and p100 Function as the Core of High-Molecular-Weight Heterogeneous Complexes

Nfkb1 and Nfkb2 proteins p105 and p100 serve both as NF-kappa B precursors and inhibitors of NF-kappa B dimers. In a biochemical characterization of endogenous cytoplasmic and purified recombinant proteins, we found that p105 and p100 assemble into high-molecular-weight complexes that contribute to the regulation of all NF-kappa B isoforms. Unlike the classical inhibitors I kappa B alpha, -beta, and -epsilon, high-molecular-weight complexes of p105 and p100 proteins bind NF-kappa B subunits in two modes: through direct dimerization of Rel homology domain-containing NF-kappa B polypeptides and through interactions of the p105 and p100 ankyrin repeats with preformed NF-kappa B dimers, thereby mediating the bona fide I kappa 3 activities, I kappa B gamma and I kappa B delta. Our biochemical evidence suggests an assembly pathway in which kinetic mechanisms control NF-kappa B dimer formation via processing and assembly of large complexes that contain I kappa B activities.