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  • Title: IRF-1-binding site in the first intron mediates interferon-γ-induced optineurin promoter activation.
    Author: Sudhakar C, Vaibhava V, Swarup G.
    Journal: Biochem Biophys Res Commun; 2013 Jul 19; 437(1):179-84. PubMed ID: 23811275.
    Abstract:
    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.
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