Diverse molecular mechanisms of inhibition of NF-kappa B/DNA binding complexes by I kappa B proteins

Gene Expr. 1993;3(2):135-50.

Abstract

The activity of the rel/NF-kappa B/dorsal family of kappa B site binding proteins is regulated by I kappa B proteins. The ankyrin repeat motif identified I kappa B family members, which include I kappa B alpha (pp40/MAD-3), I kappa B gamma, and bcl3, directly associated with kappa B site binding proteins, resulting in specific DNA-binding inhibition of rel, p50, or p65 dimers. We report that I kappa B gamma, containing eight ankyrin repeats, mediates a reversible inhibition of (p50)2-DNA complex but cannot displace preformed DNA-protein complexes. I kappa B alpha and bcl3, on the other hand, can displace preformed DNA-protein complexes. I kappa B alpha specifically displaces (p65)2 or p50/p65-DNA complexes but requires the C-terminal 37 amino acids in addition to the ankyrin repeat domain. Human bcl3 protein specifically displaces (p50)2-DNA complexes. Because I kappa B alpha and bcl3 can displace preformed (p65)2 or (p50)2-DNA complexes, respectively, we propose that they can act as repressors or antirepressors of NF-kappa B-induced gene expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ankyrins / genetics
  • B-Cell Lymphoma 3 Protein
  • Base Sequence
  • Binding Sites
  • DNA / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Repetitive Sequences, Nucleic Acid
  • Signal Transduction
  • Transcription Factor RelB
  • Transcription Factors*

Substances

  • Ankyrins
  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Bcl3 protein, mouse
  • NF-kappa B
  • Proto-Oncogene Proteins
  • RELB protein, human
  • Relb protein, mouse
  • Transcription Factors
  • Transcription Factor RelB
  • DNA