Journal
NATURE IMMUNOLOGY
Volume 11, Issue 6, Pages 487-U50Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1876
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Funding
- National Natural Science Foundation of China [30825036, 30721091]
- National Key Basic Research Program of China [2007CB512403]
- National Grand Program on Key Infectious Disease [2009ZX10004-309]
- Ministry of Education of China [NCET-07-0143]
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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.
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