Identification of novel co-repressor molecules for Interferon Regulatory Factor-2.
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.
Childs
Kay S
KS
Department of Biochemistry and Immunology, St George's Hospital Medical School, University of London, London SW17 0RE, UK.
Goodbourn
Stephen
S
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D050836:Interferon Regulatory Factor-2; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; C494229:IRF2 protein, human; C475082:IRF2BP2 protein, human; D050836:Interferon Regulatory Factor-2; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D014157:Transcription Factors; C475081:IRF2BP1 protein, human; D044767:Ubiquitin-Protein Ligases