The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators

Oncogene. 1999 Jun 3;18(22):3316-23. doi: 10.1038/sj.onc.1202717.

Abstract

The proto-oncoprotein Bcl-3 is a member of the IkappaB family and is present predominantly in the nucleus. To gain insight into specific nuclear functions of Bcl-3 we have isolated proteins that interact with its ankyrin repeat domain. Using the yeast two-hybrid-system we identified four novel binding partners of Bcl-3 in addition to NF-kappaB p50 and p52, previously known to associate with Bcl-3. The novel Bcl-3 interactors Jab1, Pirin, Tip60 and Bard1 are nuclear proteins which also bind to other transcription factors including c-Jun, nuclear factor I (NFI), HIV-1 Tat or the tumor suppressor and PolII holoenzyme component Brca1, respectively. Bcl-3, p50, and either Bard1, Tip60 or Pirin are sequestered into quarternary complexes on NF-kappaB DNA binding sites, whereas Jab1 enhances p50-Bcl-3-DNA complex formation. Furthermore, the histone acetylase Tip60 enhances Bcl-3-p50 activated transcription through an NF-kappaB binding site, indicating that quarternary complexes containing Bcl-3 interactors modulate NF-kappaB driven gene expression. These data implicate Bcl-3 as an adaptor between NF-kappaB p50/p52 and other transcription regulators and suggest that its gene activation function may at least in part be due to recruitment of the Tip60 histone actetylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases*
  • Animals
  • Ankyrins / metabolism
  • B-Cell Lymphoma 3 Protein
  • Binding Sites
  • COP9 Signalosome Complex
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dioxygenases
  • HeLa Cells / metabolism
  • Histone Acetyltransferases
  • Humans
  • I-kappa B Proteins
  • Intracellular Signaling Peptides and Proteins
  • Lysine Acetyltransferase 5
  • Mutation
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptide Hydrolases
  • Proteins / genetics
  • Proteins / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repetitive Sequences, Amino Acid
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Yeasts / genetics

Substances

  • Ankyrins
  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Dioxygenases
  • PIR protein, human
  • Acetyltransferases
  • Histone Acetyltransferases
  • KAT5 protein, human
  • Lysine Acetyltransferase 5
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex