Abstract
The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3 gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Blotting, Northern
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Cell Line
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Chloramphenicol O-Acetyltransferase / genetics
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Chloramphenicol O-Acetyltransferase / metabolism
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Cycloheximide / pharmacology
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DNA / genetics
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DNA / isolation & purification
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DNA-Binding Proteins / metabolism*
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Enhancer Elements, Genetic* / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Library
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HeLa Cells
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Humans
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Interferon Regulatory Factors
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Interferon-beta / pharmacology*
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Interferon-gamma / pharmacology*
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Lung / physiology
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Molecular Sequence Data
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Plasmids
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Promoter Regions, Genetic* / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins / metabolism
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Repressor Proteins*
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Sequence Homology, Amino Acid
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Transfection
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Tumor Cells, Cultured
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beta-Galactosidase / genetics
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beta-Galactosidase / metabolism
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Interferon Regulatory Factors
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RNA, Messenger
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Recombinant Proteins
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Repressor Proteins
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interferon regulatory factor-8
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Interferon-beta
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Interferon-gamma
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DNA
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Cycloheximide
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Chloramphenicol O-Acetyltransferase
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beta-Galactosidase
Associated data
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GENBANK/D10520
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GENBANK/D12749
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GENBANK/D12750
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GENBANK/D12751
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GENBANK/D12752
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GENBANK/D12753
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GENBANK/L01427
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GENBANK/L01429
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GENBANK/L01441
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GENBANK/M91196