title: JOSD1 Negatively Regulates Type-I Interferon Antiviral Activity by Deubiquitinating and Stabilizing SOCS1.
abstract: The Josephin domain-containing (JOSD) protein 1 (JOSD1) is recognized as one member of deubiquitinases (DUBs) due to its catalytic "Josephin" domain. However, the in vivo deubiquitinating activity of JOSD1 remains unidentified, and the biological functions of JOSD1 are largely unknown. In this study, we report that JOSD1 plays an important role in regulating type-I interferon (IFN-I)-mediated antiviral activity. JOSD1 physically interacts with SOCS1, which is an essential negative regulator of many cytokines signaling, and enhances SOCS1 stability by deubiquitinating K48-linked polyubiquitination of SOCS1. Furthermore, JOSD1 inhibits IFN-I-induced signaling pathway and antiviral response. Interestingly, during the early stage of viral infections, the levels of JOSD1 and SOCS1 undergo downregulation, which may facilitate activation of IFN-I signaling and efficient antiviral activity. Thus, our finding identified the first deubiquitinating substrate of JOSD1 and a novel biological function of JOSD1 and may provide a potential target for IFNs-based antiviral therapy.
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Liting
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 3 Department of Clinical Laboratory, Xiangya Hospital of Central South University , Changsha, China .
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Liping
authors.initials: L
authors.lastname: Qian
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Yukang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Qiao
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .
authors.forename: Wenqian
authors.initials: W
authors.lastname: Xu
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Tingting
authors.initials: T
authors.lastname: Guo
authors.affiliation: 4 Department of Oncology, The First Affiliated Hospital of Soochow University , Suzhou, China .
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Yu
authors.affiliation: 1 Institutes of Biology and Medical Sciences, Soochow University , Suzhou, China .|2 Jiangsu Key Laboratory of Infection and Immunity, Soochow University , Suzhou, China .
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D010450:Endopeptidases; D057809:HEK293 Cells; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D010450:Endopeptidases
keywords: antiviral activity; deubiquitinase; interferon