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

SummaryNfkb1 and Nfkb2 proteins p105 and p100 serve both as NF-κB precursors and inhibitors of NF-κB 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-κB isoforms. Unlike the classical inhibitors IκBα, -β, and -ɛ, high-molecular-weight complexes of p105 and p100 proteins bind NF-κB subunits in two modes: through direct dimerization of Rel homology domain-containing NF-κB polypeptides and through interactions of the p105 and p100 ankyrin repeats with preformed NF-κB dimers, thereby mediating the bona fide IκB activities, IκBγ and IκBδ. Our biochemical evidence suggests an assembly pathway in which kinetic mechanisms control NF-κB dimer formation via processing and assembly of large complexes that contain IκB activities.