Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and myb families of DNA-binding proteins

Susan A. Veals, Chris Schindler, Debra Leonard, Xin Yuan Fu, Ruedi Aebersold, James E. Darnell, David E. Levy

Research output: Contribution to journalArticle

329 Scopus citations

Abstract

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 factor (IRF) family of DNA binding proteins in the amino-terminal 117 residues of ISGF3γ. The other IRF family proteins bind DNA with a specificity related to but distinct from that of ISGF3γ. We note sequence similarities between the related regions of IRF family proteins and the imperfect tryptophan repeats which constitute the DNA-binding domain of the c-myb oncoprotein. These sequence similarities suggest that ISGF3γ and IRF proteins and the c-myb oncoprotein use a common structural motif for DNA recognition. Recombinant ISGF3γ, like the natural protein, interacted with HeLa cell ISGF3α to form the mature ISGF3 DNA-binding complex. We suggest that other IRF family members may participate in signaling pathways by interacting with as yet unidentified regulatory subunits analogous to ISGF3α.

Original languageEnglish (US)
Pages (from-to)3315-3324
Number of pages10
JournalMolecular and cellular biology
Volume12
Issue number8
DOIs
StatePublished - Aug 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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