title: USP22 is a positive regulator of NFATc2 on promoting IL2 expression.
abstract: Nuclear factor of activated T cells (NFAT) is an important regulator of T cell activation. However, the molecular mechanism whereby NFATc2 regulates IL2 transcription is not fully understood. In this study, we showed that ubiquitin-specific protease 22 (USP22), known as a cancer stem cell marker, specifically interacted with and deubiquitinated NFATc2. USP22 stabilized NFATc2 protein levels, which required its deubiquitinase activity. Consistent with these observations, depletion of USP22 in T cells reduced the expression of IL2, which is a cytokine that signifies T effector cell activation. Our findings thus unveil a previously uncharacterized positive regulator of NFATc2, suggesting that targeting the deubiquitinase activity of USP22 could have therapeutic benefit to control IL2 expression and T cell function.
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Nie
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zuojia
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Surgery, Shanghai Public Health Center, Fudan University, Shanghai 201508, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Su
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Institute for Immunity and Transplantation, Shanghai East Hospital, Tongji University, Shanghai 200120, China.
authors.forename: Jiayou
authors.initials: J
authors.lastname: Tang
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Immunology, Anhui Medical University, Hefei 230032, China.
authors.forename: Qingsi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China.
authors.forename: Jijia
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ge
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: andy@sibs.ac.cn.
authors.forename: Andy
authors.initials: A
authors.lastname: Tsun
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: binli@sibs.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D050778:NFATC Transcription Factors / Q000378:metabolism*; D025941:Protein Interaction Mapping; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000235:genetics; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D043222:Ubiquitin Thiolesterase; D054875:Ubiquitination
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D034741:RNA, Small Interfering; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human
keywords: Deubiquitinase; IL2; NFATc2; Stability; T cell; USP22