IRF-1-binding site in the first intron mediates interferon-γ-induced optineurin promoter activation
| Autor: | Cherukuri Sudhakar, Vipul Vaibhava, Ghanshyam Swarup |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
DNA Mutational Analysis
Molecular Sequence Data Biophysics Cell Cycle Proteins Biochemistry Interferon-gamma Transcription Factor TFIIIA Humans Binding site Promoter Regions Genetic Molecular Biology Transcription factor Optineurin Binding Sites Base Sequence Chemistry Tumor Necrosis Factor-alpha NF-kappa B Signal transducing adaptor protein Membrane Transport Proteins Promoter Cell Biology Molecular biology Introns IRF1 Gene Expression Regulation STAT protein Signal transduction HeLa Cells Interferon Regulatory Factor-1 Protein Binding |
| Zdroj: | Biochemical and biophysical research communications. 437(1) |
| ISSN: | 1090-2104 |
| Popis: | Optineurin is an adaptor protein involved in signal transduction, membrane vesicle trafficking and autophagy. Optineurin expression is induced by cytokines. Previously we have shown that tumor necrosis factor-α activates optineurin promoter through NF-κB-binding site in the core promoter. However, this promoter was not activated by interferon-γ. Here, we report identification of a functional IRF-1-binding site in the first intron of human optineurin gene that mediates interferon-γ-induced activation of the promoter. Optineurin promoter, containing the contiguous intronic sequences with IRF-1 responsive sites, is strongly activated by IRF-1. Mutational inactivation of IRF-1 site resulted in loss of activation of the promoter by interferon-γ and also by IRF-1. We also show that IRF-1 cooperates with NF-κB to activate optineurin promoter. The synergistic effect of these two transcription factors (IRF-1 and NF-κB) may be involved in cooperative induction of optineurin promoter by interferon-γ and tumor necrosis factor-α. |
| Databáze: | OpenAIRE |
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