The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner

Mol Cell Biol. 1993 Jun;13(6):3557-66. doi: 10.1128/mcb.13.6.3557-3566.1993.

Abstract

The product of the putative proto-oncogene bcl-3 is an I kappa B-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappa B p50 subunit and a closely related homolog, p52 (previously p49), to immunoglobulin kappa NF-kappa B DNA motifs. Bcl-3 could catalyze the removal of these proteins from DNA. At concentrations that significantly inhibited DNA binding by homodimeric p50, Bcl-3 did not inhibit binding of reconstituted heterodimeric NF-kappa B (p50:p65), a DNA-binding homodimeric form of p65, or homodimers of c-Rel. Phosphatase treatment of Bcl-3 partially inactivated its inhibitory properties, implicating a role for phosphorylation in the regulation of Bcl-3 activity. Bcl-3, like p50, localizes to the cell nucleus. In cells cotransduced with Bcl-3 and p50, both molecules could be found in the nucleus of the same cells. Interestingly, coexpression of Bcl-3 with a p50 mutant deleted for its nuclear-localizing signal resulted in the relocalization of Bcl-3 to the cytoplasm, showing that the proteins interact in the cell. These properties contrast Bcl-3 to classically defined I kappa B, which maintains heterodimeric NF-kappa B p50:p65 in the cytoplasm through specific interactions with the p65 subunit. Bcl-3 appears to be a nuclear, I kappa B-related molecule that regulates the activity of homodimeric nuclear p50 and its homolog p52.

Publication types

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

MeSH terms

  • Animals
  • B-Cell Lymphoma 3 Protein
  • Baculoviridae / genetics
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / genetics*
  • Humans
  • I-kappa B Proteins*
  • Macromolecular Substances
  • Molecular Sequence Data
  • Molecular Weight
  • Moths
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Oligodeoxyribonucleotides
  • Oligonucleotide Probes
  • Phosphorylation
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogenes*
  • Restriction Mapping
  • Transcription Factors
  • Transfection

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • DNA-Binding Proteins
  • I kappa B beta protein
  • I-kappa B Proteins
  • MAS1 protein, human
  • Macromolecular Substances
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Oligonucleotide Probes
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Transcription Factors