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nature portfolio genome editing technologies privacy policy research genome-wide libraries health/disease status/genetic information granulocyte–macrophage colony-stimulating factor mevalonate pathway-hmg-coa reductase tamoxifen-treated cre+/−ubxn3bflox/flox mice author information authors advertising ifn-i-inducing pathways exist ifn-i-induced antiviral effector tamoxifen-inducible cre-loxp approach social media tmx-treated cre+/− ubxn3bflox/flox mock-treated cre+/− ubxn3bflox/flox multifaceted nature reprints 10 ng/ml murine gm-csf produce cre+/−ubxn3bflox/flox cyclic gmp-amp synthase tamoxifen-inducible cre model dna virus-triggered response untreated cre+ ubxn3bflox/flox sting-mediated immune responses pgl3-isre luciferase reporter nature 498 nature 455 nature 461 nature 388 nature 445 nature cre+/−ubxn3bflox/flox mouse bone marrow-derived macrophage single-stranded poly-uridine parametric/parametric mann–whitney cre+/− ubxn3bflox/flox mice single-stranded rna virus bone marrow-derived macrophages retinoic acid-inducible gene cre+/− ubxn3bflox/flox male cre+/− ubxn3bflox/flox mefs interferon-dependent innate immunity sting-mediated immune signaling anti-dna virus immunity references sun pre-warmed fresh medium low-density lipoprotein secretion scientific reports

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         headline:UBXN3B positively regulates STING-mediated antiviral immune responses
         description:The ubiquitin regulatory X domain-containing proteins (UBXNs) are likely involved in diverse biological processes. Their physiological functions, however, remain largely unknown. Here we present physiological evidence that UBXN3B positively regulates stimulator-of-interferon genes (STING) signaling. We employ a tamoxifen-inducible Cre-LoxP approach to generate systemic Ubxn3b knockout in adult mice as the Ubxn3b-null mutation is embryonically lethal. Ubxn3b−/−, like Sting−/− mice, are highly susceptible to lethal herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection, which is correlated with deficient immune responses when compared to Ubxn3b+/+ littermates. HSV-1 and STING agonist-induced immune responses are also reduced in several mouse and human Ubxn3b−/− primary cells. Mechanistic studies demonstrate that UBXN3B interacts with both STING and its E3 ligase TRIM56, and facilitates STING ubiquitination, dimerization, trafficking, and consequent recruitment and phosphorylation of TBK1. These results provide physiological evidence that links the UBXN family with antiviral immune responses. The UBXN proteins are likely involved in a diverse range of biological processes, but their physiological functions remain largely unknown. Here the authors show that UBXN3B positively regulates STING-mediated immune responses in the context of viral infections.
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      description:The ubiquitin regulatory X domain-containing proteins (UBXNs) are likely involved in diverse biological processes. Their physiological functions, however, remain largely unknown. Here we present physiological evidence that UBXN3B positively regulates stimulator-of-interferon genes (STING) signaling. We employ a tamoxifen-inducible Cre-LoxP approach to generate systemic Ubxn3b knockout in adult mice as the Ubxn3b-null mutation is embryonically lethal. Ubxn3b−/−, like Sting−/− mice, are highly susceptible to lethal herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection, which is correlated with deficient immune responses when compared to Ubxn3b+/+ littermates. HSV-1 and STING agonist-induced immune responses are also reduced in several mouse and human Ubxn3b−/− primary cells. Mechanistic studies demonstrate that UBXN3B interacts with both STING and its E3 ligase TRIM56, and facilitates STING ubiquitination, dimerization, trafficking, and consequent recruitment and phosphorylation of TBK1. These results provide physiological evidence that links the UBXN family with antiviral immune responses. The UBXN proteins are likely involved in a diverse range of biological processes, but their physiological functions remain largely unknown. Here the authors show that UBXN3B positively regulates STING-mediated immune responses in the context of viral infections.
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            name:New York Medical College
            address:
               name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
               type:PostalAddress
            type:Organization
      name:Dana G. Mordue
      affiliation:
            name:New York Medical College
            address:
               name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
               type:PostalAddress
            type:Organization
      name:Toyoshi Fujimoto
      affiliation:
            name:Nagoya University Graduate School of Medicine
            address:
               name:Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
               type:PostalAddress
            type:Organization
      name:Gong Cheng
      affiliation:
            name:Tsinghua University
            address:
               name:Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Fuping You
      affiliation:
            name:Peking University Health Science Center
            address:
               name:Beijing Key Laboratory of Tumor Systems Biology, Department of Immunology, School of Basic Medical Sciences, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China
               type:PostalAddress
            type:Organization
      name:Rongtuan Lin
      affiliation:
            name:McGill University
            address:
               name:Lady Davis Institute-Jewish General Hospital, Department of Medicine, McGill University, Montreal, Canada
               type:PostalAddress
            type:Organization
      name:Erol Fikrig
      affiliation:
            name:Yale University School of Medicine
            address:
               name:Section of Infectious Diseases, Yale University School of Medicine, New Haven, USA
               type:PostalAddress
            type:Organization
            name:Howard Hughes Medical Institute
            address:
               name:Howard Hughes Medical Institute, Chevy Chase, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Penghua Wang
      affiliation:
            name:New York Medical College
            address:
               name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
      name:Lady Davis Institute-Jewish General Hospital, Department of Medicine, McGill University, Montreal, Canada
      name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
      name:Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang City, China
      name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
      name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
      name:College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing City, China
      name:Department of Parasitology, School of Medicine, Jinan University, Guangzhou City, China
      name:Beijing Key Laboratory of Tumor Systems Biology, Department of Immunology, School of Basic Medical Sciences, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China
      name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
      name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
      name:Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
      name:Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China
      name:Beijing Key Laboratory of Tumor Systems Biology, Department of Immunology, School of Basic Medical Sciences, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China
      name:Lady Davis Institute-Jewish General Hospital, Department of Medicine, McGill University, Montreal, Canada
      name:Section of Infectious Diseases, Yale University School of Medicine, New Haven, USA
      name:Howard Hughes Medical Institute, Chevy Chase, USA
      name:Department of Microbiology and Immunology, New York Medical College, Valhalla, USA

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