Identification of novel co-repressor molecules for Interferon Regulatory Factor-2

Nucleic Acids Res. 2003 Jun 15;31(12):3016-26. doi: 10.1093/nar/gkg431.


We have identified two novel proteins that interact specifically with the C-terminal repression domain of Interferon Regulatory Factor-2 (IRF-2). These proteins, which we term IRF-2 binding proteins 1 and 2 (IRF-2BP1 and IRF-2BP2, the latter having two splicing isoforms, A and B), are nuclear proteins, and have the properties of IRF-2-dependent transcriptional co-repressors that can inhibit both enhancer-activated and basal transcription in a manner that is not dependent upon histone deacetylation. IRF-2BP1 and IRF-2BP2A/B contain an N-terminal zinc finger and a C-terminal RING finger domain of the C3HC4 subclass, but show no homology to other known transcriptional regulators; they therefore define a new family of co- repressor proteins. An alternatively spliced form of IRF-2 that lacks two amino acids (valines 177 and 178) in the central portion of the protein (IRF-2[S]) cannot bind to these co-repressors and cannot mediate repression despite having the same C- terminal repression domain as IRF-2, suggesting that the relative conformation of the DNA binding domain and the C-terminal region of IRF-2 is crucial for transcriptional repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • DNA, Complementary / isolation & purification
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Gene Silencing
  • HeLa Cells
  • Histone Deacetylase Inhibitors
  • Humans
  • Interferon Regulatory Factor-2
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Transcription Factors*
  • Transcription, Genetic
  • Ubiquitin-Protein Ligases


  • Carrier Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • Histone Deacetylase Inhibitors
  • IRF2 protein, human
  • IRF2BP2 protein, human
  • Interferon Regulatory Factor-2
  • Nuclear Proteins
  • Protein Isoforms
  • Repressor Proteins
  • Transcription Factors
  • IRF2BP1 protein, human
  • Ubiquitin-Protein Ligases