title: Deubiquitination and stabilization of IL-33 by USP21.
abstract: Interleukin-33 (IL-33) is a dual-function protein that acts both as a secreted cytokine and as a nuclear factor regulating gene transcription. It has been demonstrated that IL-33 exerts its nuclear function in promoting the transcription of NF-κB p65. Here, we show that USP21-mediated deubiquitination of IL-33 affects the transcription of p65. IL-33 can be post-translationally modified by ubiquitination. Ubiquitin-specific protease 21 (USP21) interacts with IL-33 and also localizes in nucleus. The protein stability of IL-33 is maintained by USP21 through deubiquitination. Furthermore, depletion of USP21 reduces IL-33 protein levels and IL-33-mediated NF-κB p65 promoter activity. Our findings reveal the role of ubiquitination modification in regulating the protein stability and the nuclear function of IL-33.
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China.
authors.forename: Lianqin
authors.initials: L
authors.lastname: Tao
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai 200031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai 200031, China.
authors.forename: Miranda
authors.initials: M
authors.lastname: Piccioni
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China.
authors.forename: Guochao
authors.initials: G
authors.lastname: Shi
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai 200031, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D055550:Protein Stability; D014162:Transfection; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; C408875:USP21 protein, human; D043222:Ubiquitin Thiolesterase
keywords: IL-33; USP21; deubiquitinase; stability