Institute of Immunology, Second Military Medical University, Shanghai, China.
Nat Immunol. 2010 Jun;11(6):487-94. doi: 10.1038/ni.1876. Epub 2010 May 9.
Intracellular nucleic acid sensors detect microbial RNA and DNA and trigger the production of type I interferon. However, the cytosolic nucleic acid-sensing system remains to be fully identified. Here we show that the cytosolic nucleic acid-binding protein LRRFIP1 contributed to the production of interferon-beta (IFN-beta) induced by vesicular stomatitis virus (VSV) and Listeria monocytogenes in macrophages. LRRFIP1 bound exogenous nucleic acids and increased the expression of IFN-beta induced by both double-stranded RNA and double-stranded DNA. LRRFIP1 interacted with beta-catenin and promoted the activation of beta-catenin, which increased IFN-beta expression by binding to the C-terminal domain of the transcription factor IRF3 and recruiting the acetyltransferase p300 to the IFN-beta enhanceosome via IRF3. Therefore, LRRFIP1 and its downstream partner beta-catenin constitute another coactivator pathway for IRF3-mediated production of type I interferon.
细胞内核酸传感器可检测微生物 RNA 和 DNA，并触发 I 型干扰素的产生。然而，细胞溶质核酸感应系统仍有待完全确定。在这里，我们表明细胞质核酸结合蛋白 LRRFIP1 有助于巨噬细胞中水疱性口炎病毒 (VSV) 和李斯特菌诱导的干扰素-β (IFN-β) 的产生。LRRFIP1 结合外源性核酸，并增加双链 RNA 和双链 DNA 诱导的 IFN-β 的表达。LRRFIP1 与β-连环蛋白相互作用，并促进β-连环蛋白的激活，通过与转录因子 IRF3 的 C 末端结构域结合并通过 IRF3 将乙酰转移酶 p300 募集到 IFN-β 增强子复合物，从而增加 IFN-β 的表达。因此，LRRFIP1 和其下游伴侣β-连环蛋白构成了 IRF3 介导的 I 型干扰素产生的另一个共激活途径。
