The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33

• Main Authors: Yingmeng Ni, Lianqin Tao, Chen Chen, Huihui Song, Zhiyuan Li, Yayi Gao, Jia Nie, Miranda Piccioni, Guochao Shi, Bin Li
• Format: Article
• Language: English
• Published: MDPI AG 2015-11-01
• Series: International Journal of Molecular Sciences
• Subjects: IL-33; ubiquitin-specific protease 17 (USP17); IL-13; DNA binding; deubiquitinase
• Online Access: http://www.mdpi.com/1422-0067/16/11/26063

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.