The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway.
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.
Yang
Pengyuan
P
Institute of Immunology, Second Military Medical University, Shanghai, China.
An
Huazhang
H
Liu
Xingguang
X
Wen
Mingyue
M
Zheng
Yuanyuan
Y
Rui
Yaocheng
Y
Cao
Xuetao
X
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003600:Cytosol / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
D004279:DNA, Viral; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; C494233:Irf3 protein, mouse; C114370:LRRFIP1 protein, human; D016601:RNA-Binding Proteins; D051192:Receptors, Pattern Recognition; D051176:beta Catenin
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