Autocrine Amplification of Type I Interferon Gene Expression Mediated by Interferon Stimulated Gene Factor 3 (ISGF3)

• Published in: Journal of biochemistry (Tokyo) 1996-07, Vol.120 (1), p.160-169
• Main Authors: Yoneyama, Mitsutoshi, Suhara, Wakako, Fukuhara, Yukiko, Sato, Mayumi, Ozato, Keiko, Fujita, Takashi
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; DNA - metabolism; DNA Methylation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - pharmacology; Feedback; Gene Expression Regulation - genetics; gene regulation; Interferon Regulatory Factor-1; Interferon Regulatory Factor-2; Interferon Type I - genetics; Interferon Type I - physiology; Interferon-Stimulated Gene Factor 3; Interferon-Stimulated Gene Factor 3, gamma Subunit; IRF; ISGF3; L Cells (Cell Line); Mice; Newcastle disease virus - growth & development; Phosphoproteins - metabolism; Promoter Regions, Genetic - genetics; Recombinant Fusion Proteins; Repressor Proteins; RNA, Messenger - analysis; Sequence Deletion; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - pharmacology; type I interferon; viral induction; Virus Activation
• ISSN: 0021-924X
• DOI: 10.1093/oxfordjournals.jbchem.a021379

Interferon regulatory factor (IRF)-1 and IRF-2 have been implicated for the virus-induced expression of the interferon-α and β (type I IFN) genes. However, recent gene disruption studies in mice suggested the presence of other factor(s) interacting with overlapping promoter elements. In the present paper, we describe the characterization of a DNA binding factor which is strongly induced after virus infection and recognizes these promoter elements. After extensive purification, the factor was revealed to be identical to IFN-stimulated gene factor 3 (ISGF3), a transcription factor complex activated by IFN treatment. ISGF3 binds to the promoter element of IFN-β positive regulatory domain I (PRDI), with significantly higher affinity than IRF-1, 2, and mutational analysis of PRDI showed that the gene expression and binding of ISGF3, but not of IRF-1, 2, are highly correlated. Furthermore, our functional analysis involving a dominant negative inhibitor for ISGF3 activation and an anti-IFN neutralizing antibody clearly demonstrated the presence of a positive feedback pathway for type I IFN genes mediated by ISGF3.