title: The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33.
abstract: IL-33 is a new member of the IL-1 family cytokines, which is expressed by different types of immune cells and non-immune cells. IL-33 is constitutively expressed in the nucleus, where it can act as a transcriptional regulator. So far, no direct target for nuclear IL-33 has been identified, and the regulation of IL-33 nuclear function remains largely unclear. Here, we report that the transcription of type 2 inflammatory cytokine IL-13 is positively regulated by nuclear IL-33. IL-33 can directly bind to the conserved non-coding sequence (CNS) before the translation initiation site in the IL13 gene locus. Moreover, IL-33 nuclear function and stability are regulated by the enzyme ubiquitin-specific protease 17 (USP17) through deubiquitination of IL-33 both at the K48 and at the K63 sites. Our data suggest that IL13 gene transcription can be directly activated by nuclear IL-33, which is negatively regulated by the deubiquitinase USP17.
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. danielle_mengmeng@hotmail.com.
authors.forename: Yingmeng
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. tlq.1988@163.com.
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. chenchen01@sibs.ac.cn.
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. shh_2012@hotmail.com.
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. lizhiyuan01@gmail.com.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
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. yygao@sibs.ac.cn.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Gao
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. niejia@sibs.ac.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Nie
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. pimiri@inwind.it.
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. shiguochao@hotmail.com.
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. binli@sibs.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D056426:Genetic Loci; D057809:HEK293 Cells; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D018793:Interleukin-13; D000067596:Interleukin-33; D010450:Endopeptidases; C484854:USP17L2 protein, human
keywords: DNA binding; IL-13; IL-33; deubiquitinase; ubiquitin-specific protease 17 (USP17)