BCoR, a novel corepressor involved in BCL-6 repression

Genes Dev. 2000 Jul 15;14(14):1810-23.

Abstract

BCL-6 encodes a POZ/zinc finger transcriptional repressor that is required for germinal center formation and may influence apoptosis. Aberrant expression of BCL-6 due to chromosomal translocations is implicated in certain subtypes of non-Hodgkin's lymphoma. The POZ domains of BCL-6 and several other POZ proteins interact with corepressors N-CoR and SMRT. Here we identify and characterize a novel corepressor BCoR (BCL-6 interacting corepressor), which is expressed ubiquitously in human tissues. BCoR can function as a corepressor when tethered to DNA and, when overexpressed, can potentiate BCL-6 repression. Specific class I and II histone deacetylases (HDACs) interact in vivo with BCoR, suggesting that BCoR may functionally link these two classes of HDACs. Strikingly, BCoR interacts selectively with the POZ domain of BCL-6 but not with eight other POZ proteins tested, including PLZF. Additionally, interactions between the BCL-6 POZ domain and SMRT, N-CoR, and BCoR are mutually exclusive. The specificity of the BCL-6/BCoR interaction suggests that BCoR may have a role in BCL-6-associated lymphomas.

Publication types

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

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Cell Line
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Genes, Reporter
  • HeLa Cells
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Humans
  • Luciferases / metabolism
  • Molecular Sequence Data
  • Plasmids
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Repressor Proteins / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • BCOR protein, human
  • DNA, Complementary
  • DNA-Binding Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins
  • Transcription Factors
  • Luciferases
  • Histone Deacetylases