title: Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
authors.forename: Soonhwa
authors.initials: S
authors.lastname: Song
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
authors.forename: Jae-Jin
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
authors.forename: Jeong Yoon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea kjl@ewha.ac.kr.
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016899:Interferon-beta / Q000096:biosynthesis*; D010766:Phosphorylation; D011070:Poly I-C / Q000378:metabolism; D040081:Protein Array Analysis; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C490780:FAF1 protein, human; C107940:IPO5 protein, human; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D025801:Ubiquitin; D028961:beta Karyopherins; D016899:Interferon-beta; D011070:Poly I-C
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