title: Ubiquitin-dependent Turnover of Adenosine Deaminase Acting on RNA 1 (ADAR1) Is Required for Efficient Antiviral Activity of Type I Interferon.
abstract: Adenosine deaminase acting on RNA 1 (ADAR1) catalyzes RNA editing of cellular and viral RNAs. Besides RNA editing, ADAR1 has recently been shown to play important roles in maintaining the body balance, including tissue homoeostasis, organ development, and autoimmune regulations, by inhibiting both IFN production and subsequent IFN-activated pathways. Accordingly, the question was raised how IFN signaling induced by viral infections overcomes the inhibitory effect of constitutively expressed ADAR1 (ADAR1-P110) to execute efficient antiviral activity. Here we unexpectedly found that IFN signaling promoted Lys48-linked ubiquitination and degradation of ADAR1-P110. Furthermore, we identified the E3 ligase β transducin repeat-containing protein responsible for IFN-mediated ADAR1-P110 down-regulation. IFN signaling promoted the interaction between β transducin repeat-containing protein and ADAR1-P110 as well as protein turnover of ADAR1-P110. Moreover, we found that both lysine 574 and 576 are essential for ADAR1-P110 ubiquitination. Critically, we demonstrated that down-regulation of ADAR1-P110 is required for IFN signaling to execute efficient antiviral activity during viral infections. These findings renew the understanding of the mechanisms by which IFN signaling acts to achieve antiviral functions and may provide potential targets for IFN-based antiviral therapy.
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Lemin
authors.initials: L
authors.lastname: Li
authors.affiliation: the Institutes of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province 215025, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Qian
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Yukang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Tingting
authors.initials: T
authors.lastname: Guo
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and.
authors.forename: Liting
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China and huizheng@suda.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D007370:Interferon Type I; D016601:RNA-Binding Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C000595356:ADAR protein, human; D000243:Adenosine Deaminase
keywords: ADAR1; E3 ubiquitin ligase; antiviral immunity; innate immunity; interferon; protein degradation; ubiquitylation (ubiquitination)