title: The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes.
abstract: Nfkb1 and Nfkb2 proteins p105 and p100 serve both as NF-kappaB precursors and inhibitors of NF-kappaB 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-kappaB isoforms. Unlike the classical inhibitors IkappaBalpha, -beta, and -epsilon, high-molecular-weight complexes of p105 and p100 proteins bind NF-kappaB subunits in two modes: through direct dimerization of Rel homology domain-containing NF-kappaB polypeptides and through interactions of the p105 and p100 ankyrin repeats with preformed NF-kappaB dimers, thereby mediating the bona fide IkappaB activities, IkappaBgamma and IkappaBdelta. Our biochemical evidence suggests an assembly pathway in which kinetic mechanisms control NF-kappaB dimer formation via processing and assembly of large complexes that contain IkappaB activities.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Savinova
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Gourisankar
authors.initials: G
authors.lastname: Ghosh
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D052003:NF-kappa B p52 Subunit / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; C489548:NFKB1 protein, human; C498206:NFKB2 protein, human; D011498:Protein Precursors; D021122:Protein Subunits