The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes

Mol Cell. 2009 Jun 12;34(5):591-602. doi: 10.1016/j.molcel.2009.04.033.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Line
  • Dimerization
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit / chemistry
  • NF-kappa B p50 Subunit / metabolism
  • NF-kappa B p50 Subunit / physiology*
  • NF-kappa B p52 Subunit / chemistry
  • NF-kappa B p52 Subunit / metabolism
  • NF-kappa B p52 Subunit / physiology*
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism
  • Protein Precursors / physiology
  • Protein Structure, Tertiary
  • Protein Subunits / metabolism
  • Sequence Alignment


  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NF-kappa B p52 Subunit
  • NFKB1 protein, human
  • NFKB2 protein, human
  • Protein Precursors
  • Protein Subunits