Identification of a new interferon-alpha/beta-inducible DNA-binding protein that interacts with the regulatory element A of 2',5'-oligoadenylate synthetase ME-12 gene.
A new interferon (IFN)-stimulated response factor (ISRF) has been identified in nuclear extracts of IFN-alpha/beta-treated murine BALB/c-3T3 fibroblasts by the mobility-shift electrophoresis assay. The factor, ISRF-2, displays murine 2',5'-oligoadenylate (2-5A) synthetase ME-12 gene 5' regulatory element A specificity and differs from the previously described IFN response element B-specific factor ISRF-1 in several aspects. ISRF-2 is restricted to the nucleus, whereas ISRF-1 exists in the cytoplasm and translocates into the nucleus upon treatment of cells with IFN-alpha/beta. The ionic strength requirement of ISRF-2 for maximal DNA-binding activity is lower than that of ISRF-1. The DNA-binding activity of ISRF-2, but not that of ISRF-1, is markedly suppressed by Mg2+. In common with ISRF-1, the phosphorylated form of ISRF-2 appears to be required for DNA-binding activity. A model is proposed for the mechanism whereby murine IFN-alpha/beta regulates 2-5A synthetase ME-12 gene expression.
Yan
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C
Rockefeller University, New York, NY 10021.
Tamm
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D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D029867:Xenopus Proteins
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; C494230:Irf2 protein, mouse; D012097:Repressor Proteins; C081930:Tfam protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C097078:XL-MTTFA protein, Xenopus; D029867:Xenopus Proteins; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase