title: p53 degradation by a coronavirus papain-like protease suppresses type I interferon signaling.
abstract: Infection by human coronaviruses is usually characterized by rampant viral replication and severe immunopathology in host cells. Recently, the coronavirus papain-like proteases (PLPs) have been identified as suppressors of the innate immune response. However, the molecular mechanism of this inhibition remains unclear. Here, we provide evidence that PLP2, a catalytic domain of the nonstructural protein 3 of human coronavirus NL63 (HCoV-NL63), deubiquitinates and stabilizes the cellular oncoprotein MDM2 and induces the proteasomal degradation of p53. Meanwhile, we identify IRF7 (interferon regulatory factor 7) as a bona fide target gene of p53 to mediate the p53-directed production of type I interferon and the innate immune response. By promoting p53 degradation, PLP2 inhibits the p53-mediated antiviral response and apoptosis to ensure viral growth in infected cells. Thus, our study reveals that coronavirus engages PLPs to escape from the innate antiviral response of the host by inhibiting p53-IRF7-IFNβ signaling.
authors.affiliation: From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China, the Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province 116044, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: the Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China, and.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Song
authors.affiliation: From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tian
authors.affiliation: From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Guichun
authors.initials: G
authors.lastname: Xing
authors.affiliation: the Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China, and.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: the School of Life Sciences, Sichuan University, Sichuan Province, 610065, China.
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Xiao
authors.affiliation: From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China, the Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province 116044, China, zhanglq@nic.bmi.ac.cn.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D017934:Coronavirus / Q000201:enzymology*; D006801:Humans; D047468:Immunoprecipitation; D007370:Interferon Type I / Q000378:metabolism*; D010206:Papain / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D010447:Peptide Hydrolases; D010206:Papain
keywords: Coronavirus; Innate Immunity; Interferon; Mouse Double Minute 2 Homolog (MDM2); PLP2; Virus; p53