title: The E3 deubiquitinase USP17 is a positive regulator of retinoic acid-related orphan nuclear receptor γt (RORγt) in Th17 cells.
abstract: Stable retinoic acid-related orphan nuclear receptor γt (RORγt) expression is pivotal for the development and function of Th17 cells. Here we demonstrate that expression of the transcription factor RORγt can be regulated through deubiquitination, which prevents proteasome-mediated degradation. We establish that USP17 stabilizes RORγt protein expression by reducing RORγt polyubiquitination at its Lys-360 residue. In contrast, knockdown of endogenous USP17 in Th17 cells resulted in decreased RORγt protein levels and down-regulation of Th17-related genes. Furthermore, USP17 expression was up-regulated in CD4(+) T cells from systemic lupus erythematosus patients. Our data reveal a molecular mechanism in which RORγt expression in Th17 cells can be positively regulated by USP17, thereby modulating Th17 cell functions.
authors: From the Division of Rheumatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
authors: Lei
authors: L
authors: Han
authors: the Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors: Jing
authors: J
authors: Yang
authors: From the Division of Rheumatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
authors: Xiuwen
authors: X
authors: Wang
authors: the Department of Immunology, Anhui Medical University, Hefei 230032, China.
authors: Qingsi
authors: Q
authors: Wu
authors: the Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors: Shuying
authors: S
authors: Yin
authors: the Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors: Zhiyuan
authors: Z
authors: Li
authors: the Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors: Jing
authors: J
authors: Zhang
authors: the Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors: Yue
authors: Y
authors: Xing
authors: the Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors: Zuojia
authors: Z
authors: Chen
authors: From the Division of Rheumatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
authors: Andy
authors: A
authors: Tsun
authors: From the Division of Rheumatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
authors: Dan
authors: D
authors: Li
authors: From the Division of Rheumatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
authors: Miranda
authors: M
authors: Piccioni
authors: the Department of Obstetrics and Gynecology and.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University Medical School, 1630 Dongfang Road, Shanghai 200127, China.
authors: Qiang
authors: Q
authors: Guo
authors: the Department of Rheumatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China, and.
authors: Lindi
authors: L
authors: Jiang
authors: the Department of Pathology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756.
authors: Liming
authors: L
authors: Bao
authors: From the Division of Rheumatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China, huashanlvling@sina.com.
authors: Ling
authors: L
authors: Lv
authors: the Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China, binli@sibs.ac.cn.
authors: Bin
authors: B
authors: Li
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D010450:Endopeptidases; C484854:USP17L2 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Autoimmune Disease; Deubiquitination; RORγt; Systemic Lupus Erythematosus; T Cell Biology; Th17 Cells; Transcription Factor; USP17; Ubiquitin-dependent Protease