Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus

Molecular and Cellular Biology
Soonhwa SongKong-Joo Lee

Abstract

This study is designed to examine the cellular functions of human Fas-associated factor 1 (FAF1) containing multiple ubiquitin-related domains. Microarray analyses revealed that interferon-stimulated genes related to the antiviral response are significantly increased in FAF1-knockdown HeLa cells. Silencing FAF1 enhanced the poly(I·C)- and respiratory syncytial virus (RSV)-induced production of type I interferons (IFNs), the target genes of interferon regulator factor 3 (IRF3). IRF3 is a key transcription factor in IFN-β signaling responsible for the host innate immune response. This study also found that FAF1 and IRF3 physically associate with IPO5/importin-β3 and that overexpression of FAF1 reduces the interaction between IRF3 and IPO5/importin-β3. These findings suggest that FAF1 negatively regulates IRF3-mediated IFN-β production and the antiviral innate immune response by regulating nuclear translocation of IRF3. We conclude that FAF1 plays a novel role in negatively regulating virus-induced IFN-β production and the antiviral response by inhibiting the translocation of active, phosphorylated IRF3 from the cytosol to the nucleus.

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Citations

Feb 13, 2018·The Journal of Reproduction and Development·Hui PengTianfang Xiao
Apr 22, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takuya SueyoshiTaro Kawai
May 29, 2018·The Journal of Biological Chemistry·Rebecca L AmbroseCameron R Stewart
Jun 8, 2017·Frontiers in Cellular and Infection Microbiology·Shengyu WangMeilin Jin
Sep 29, 2020·Aging·Xiangan LinHailiang Zhang
May 23, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Harshada KetkarPenghua Wang
Sep 1, 2021·Journal of Cellular and Molecular Medicine·Fei-Fei GaoGuang-Ho Cha

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Datasets Mentioned

BETA
GSE71665

Methods Mentioned

BETA
nuclear translocation
transfection
electrophoresis
chip
PCR
GTPase
immunoprecipitation
fluorescence microscopy
confocal microscopy

Software Mentioned

ImageJ
Gene Expression Module
Luc
pISRE
Illumina GenomeStudio
Ingenuity Pathway Analysis ( IPA )

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