Identification of a New Interferon-α/β-Inducible DNA-Binding Protein That Interacts with the Regulatory Element A of 2′,5′-01igoadenylate Synthetase ME-12 Gene

Abstract

A new interferon (IFN)-stimulated response factor (ISRF) has been identified in nuclear extracts of IFN-α/β-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-α/β. 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-α/β regulates 2-5A synthetase ME-12 gene expression.