Fas-associated factor 1 negatively regulates the antiviral immune response by inhibiting translocation of interferon regulatory factor 3 to the nucleus

Soonhwa Song, Jae Jin Lee, Hee Jung Kim, Jeong Yoon Lee, Jun Chang, Kong Joo Lee

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

This study is designed to examine the cellular functions of human Fas-associated factor 1 (FAF1) containing multiple ubiquitinrelated 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.

Original languageEnglish
Pages (from-to)1136-1151
Number of pages16
JournalMolecular and Cellular Biology
Volume36
Issue number7
DOIs
StatePublished - 1 Apr 2016

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