title: Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis.
abstract: Expression of the Type I IFN (i.e., IFN-alpha s and IFN-beta) genes is efficiently induced by viruses at the transcriptional level. This induction is mediated by at least two types of positive regulatory elements located in the human IFN-beta gene promoter: (1) the repeated elements which bind both the transcriptional activator IRF-1 and the repressor IRF-2 (IRF-elements; IRF-Es), and (2) the kappa B element (kappa B-E), which binds NF kappa B and is located between the IRF-Es and the TATA box. In this study we demonstrate that a promoter containing synthetic IRF-E, which displays high affinity for the IRFs can be efficiently activated by Newcastle disease virus (NDV). In contrast, such activation was either very weak or nil when cells were treated by IFN-beta or tumor necrosis factor-alpha (TNF-alpha), despite the fact they both efficiently induce de novo synthesis of the short-lived IRF-1 in L929 cells. In fact, efficient activation of the IRF-E apparently requires an event in addition to de novo IRF-1 induction, which can be elicited by NDV even in the presence of protein synthesis inhibitor, cycloheximide. Moreover, efficient activation of the IRF-E by NDV is specifically inhibited by the protein kinase inhibitor, Staurosporin. Hence our results suggest the importance of IRF-1 synthesis and post-translational modification event(s), possibly phosphorylation for the efficient activation of IRF-Es, which are otherwise under negative regulation by IRF-2.
authors.affiliation: Institute for Molecular and Cellular Biology, Osaka University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: J
authors.initials: J
authors.lastname: Sakakibara
authors.forename: A G
authors.initials: AG
authors.lastname: Hovanessian
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: T
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012097:Repressor Proteins; D019311:Staurosporine; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D019311:Staurosporine