IRF-1-binding site in the first intron mediates interferon-γ-induced optineurin promoter activation.
IRF-1-binding site in the first intron mediates interferon-γ-induced optineurin promoter activation.
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DOI：
10.1016/j.bbrc.2013.06.065
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发表时间：
2013-07
影响因子：
3.1
通讯作者：
C. Sudhakar;Vipul Vaibhava;G. Swarup
中科院分区：
文献类型：
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作者：
C. Sudhakar;Vipul Vaibhava;G. Swarup
视神经磷酸酶是一种衔接蛋白，参与信号转导、膜囊泡运输和自噬。视神经磷酸酶的表达由细胞因子诱导。以前我们已经证明肿瘤坏死因子-α通过核心启动子中的NF-κ B结合位点激活视神经磷酸酶启动子。然而，该启动子不被干扰素-γ激活。在这里，我们报告的功能性IRF-1结合位点的人视神经磷酸酶基因的第一个内含子介导干扰素-γ诱导的启动子激活的鉴定。视神经磷酸酶启动子含有IRF-1反应位点的连续内含子序列，被IRF-1强烈激活。IRF-1位点的突变失活导致干扰素-γ和IRF-1对启动子的激活丧失。我们还发现IRF-1与NF-κB协同激活视神经磷酸酶启动子。这两种转录因子（IRF-1和NF-κB）的协同作用可能参与了IFN-γ和TNF-α对视神经磷酸酶启动子的协同诱导。
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.