Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
FEBS Open Bio. 2019 Aug;9(8):1413-1420. doi: 10.1002/2211-5463.12682. Epub 2019 Jul 1.
Tripartite motif-containing 14 (TRIM14) is a mitochondrial adaptor that promotes innate immune signaling and plays important roles in antiviral defense. Expression of TRIM14 is induced by interferon (IFN)-I. However, the mechanism by which IFN-I induces TRIM14 production is not yet determined. In this study, we have examined the function of TRIM14 promoter and found that a GC box and an IFN-stimulated response element (ISRE) are necessary for the basal level transcription of TRIM14. We further observed that IFN-I activates the TRIM14 promoter through the ISRE. In particular, interferon regulatory factor (IRF)-1 and IRF-2 bind to the TRIM14 promoter and activate transcription of TRIM14. Moreover, knockdown of IRF-1 reduces the stimulation of TRIM14 transcription by IFN-α, suggesting that IRF-1 is involved in the activation of TRIM14 by IFN-I. IRF-2 has little effect on IFN-α-induced TRIM14 transcription but is essential for the basal transcription of TRIM14.
三结构域蛋白 14（TRIM14）是一种线粒体衔接蛋白，可促进固有免疫信号转导，并在抗病毒防御中发挥重要作用。TRIM14 的表达受干扰素（IFN）-I 的诱导。然而，IFN-I 诱导 TRIM14 产生的机制尚不清楚。在本研究中，我们研究了 TRIM14 启动子的功能，发现 GC 盒和 IFN 刺激反应元件（ISRE）是 TRIM14 基础转录所必需的。我们进一步观察到 IFN-I 通过 ISRE 激活 TRIM14 启动子。具体而言，干扰素调节因子（IRF）-1 和 IRF-2 结合到 TRIM14 启动子上，激活 TRIM14 的转录。此外，IRF-1 的敲低减少了 IFN-α对 TRIM14 转录的刺激，表明 IRF-1 参与了 IFN-I 对 TRIM14 的激活。IRF-2 对 IFN-α诱导的 TRIM14 转录几乎没有影响，但对 TRIM14 的基础转录是必需的。
