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Alpha interferon stimulates transcription by converting the positive transcriptional regulator ISGF3 from a latent to an active form. This receptor-mediated event occurs in the cytoplasm, with subsequent translocation of the activated factor to the nucleus. ISGF3 has two components, termed ISGF3α and ISGF3γ. ISGF3γ serves as the DNA recognition subunit, while ISGF3α, which appears to consist of three polypeptides, is a target for alpha interferon signaling and serves as a regulatory component whose activation is required to form ISGF3. ISGF3γ DNA-binding activity was identified as a 48-kDa polypeptide, and partial amino acid sequence has allowed isolation of cDNA clones. ISGF3γ translated in vitro from recombinant clones bound DNA with a specificity indistinguishable from that of ISGF3γ purified from HeLa cells. Sequencing of ISGF3γ cDNA clones revealed significant similarity to the interferon regulatory …