The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33
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 r...
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2015-11-01
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author | Yingmeng Ni Lianqin Tao Chen Chen Huihui Song Zhiyuan Li Yayi Gao Jia Nie Miranda Piccioni Guochao Shi Bin Li |
author_facet | Yingmeng Ni Lianqin Tao Chen Chen Huihui Song Zhiyuan Li Yayi Gao Jia Nie Miranda Piccioni Guochao Shi Bin Li |
author_sort | Yingmeng Ni |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-49d7e865ae644e309e64725cd1c8ce292022-12-22T02:56:31ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-11-011611279562796610.3390/ijms161126063ijms161126063The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33Yingmeng Ni0Lianqin Tao1Chen Chen2Huihui Song3Zhiyuan Li4Yayi Gao5Jia Nie6Miranda Piccioni7Guochao Shi8Bin Li9Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaKey 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, ChinaDepartment of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaDepartment of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaKey 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, ChinaIL-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.http://www.mdpi.com/1422-0067/16/11/26063IL-33ubiquitin-specific protease 17 (USP17)IL-13DNA bindingdeubiquitinase |
spellingShingle | Yingmeng Ni Lianqin Tao Chen Chen Huihui Song Zhiyuan Li Yayi Gao Jia Nie Miranda Piccioni Guochao Shi Bin Li The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33 International Journal of Molecular Sciences IL-33 ubiquitin-specific protease 17 (USP17) IL-13 DNA binding deubiquitinase |
title | The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33 |
title_full | The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33 |
title_fullStr | The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33 |
title_full_unstemmed | The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33 |
title_short | The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33 |
title_sort | deubiquitinase usp17 regulates the stability and nuclear function of il 33 |
topic | IL-33 ubiquitin-specific protease 17 (USP17) IL-13 DNA binding deubiquitinase |
url | http://www.mdpi.com/1422-0067/16/11/26063 |
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