title: USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1.
abstract: Autophagy, mediated by a number of autophagy-related (ATG) proteins, plays an important role in the bulk degradation of cellular constituents. Beclin-1 (also known as Atg6 in yeast) is a core protein essential for autophagic initiation and other biological processes. The activity of Beclin-1 is tightly regulated by multiple post-translational modifications, including ubiquitination, yet the molecular mechanism underpinning its reversible deubiquitination remains poorly defined. Here, we identified ubiquitin-specific protease 19 (USP19) as a positive regulator of autophagy, but a negative regulator of type I interferon (IFN) signaling.USP19 stabilizes Beclin-1 by removing the K11-linked ubiquitin chains of Beclin-1 at lysine 437. Moreover, we foundthat USP19 negatively regulates type IIFNsignaling pathway, by blockingRIG-I-MAVSinteraction in a Beclin-1-dependent manner. Depletion of eitherUSP19 or Beclin-1 inhibits autophagic flux and promotes type IIFNsignaling as well as cellular antiviral immunity. Our findings reveal novel dual functions of theUSP19-Beclin-1 axis by balancing autophagy and the production of type IIFNs.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shouheng
authors.initials: S
authors.lastname: Jin
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Tian
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chuanxia
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Xie
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China Department of Experimental Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China cuij5@mail.sysu.edu.cn rwang3@houstonmethodist.org.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0002-8000-3708
authors.initials: J
authors.lastname: Cui
authors.affiliation: Houston Methodist Research Institute, Houston, TX, USA cuij5@mail.sysu.edu.cn rwang3@houstonmethodist.org.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D002460:Cell Line / Q000821:virology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity; D007370:Interferon Type I / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055550:Protein Stability; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000502:physiology; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D007370:Interferon Type I; C505371:MAVS protein, human; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D010450:Endopeptidases; C559917:USP19 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D008239:Lysine
keywords: Beclin‐1; autophagy; cross talk; type I interferon; ubiquitination