title: USP4 positively regulates RIG-I-mediated antiviral response through deubiquitination and stabilization of RIG-I.
abstract: Protein ubiquitination plays an essential role in the regulation of retinoic acid-inducible gene I (RIG-I) activation and the antiviral immune response. However, the function of the opposite process of deubiquitination in RIG-I activation remains elusive. In this study, we have identified the deubiquitinating enzyme ubiquitin-specific protease 4 (USP4) as a new regulator for RIG-I activation through deubiquitination and stabilization of RIG-I. USP4 expression was attenuated after virus-induced RIG-I activation. Overexpression of USP4 significantly enhanced RIG-I protein expression and RIG-I-triggered beta interferon (IFN-β) signaling and, at the same time, inhibited vesicular stomatitis virus (VSV) replication. Small interfering RNA (siRNA) knockdown of USP4 expression had an opposite effect. Furthermore, USP4 was found to interact with RIG-I and remove K48-linked polyubiquitination chains from RIG-I. Therefore, we identified USP4 as a new positive regulator for RIG-I that acts through deubiquitinating K48-linked ubiquitin chains and stabilizing RIG-I.
authors: Key Laboratory for Experimental Teratology of the Ministry of Education & Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Lijuan
authors: L
authors: Wang
authors: Wei
authors: W
authors: Zhao
authors: Meng
authors: M
authors: Zhang
authors: Peng
authors: P
authors: Wang
authors: Kai
authors: K
authors: Zhao
authors: Xueying
authors: X
authors: Zhao
authors: Shangru
authors: S
authors: Yang
authors: Chengjiang
authors: C
authors: Gao
mesh_terms: D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D059748:Proteolysis; D011971:Receptors, Immunologic; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000276:immunology / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases; D018116:Vesiculovirus / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
chemical_list: D011971:Receptors, Immunologic; C486203:USP4 protein, human; D025801:Ubiquitin; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
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