Ni Yingmeng, Tao Lianqin, Chen Chen, Song Huihui, Li Zhiyuan, Gao Yayi, Nie Jia, Piccioni Miranda, Shi Guochao, Li Bin
Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
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.
Int J Mol Sci. 2015 Nov 24;16(11):27956-66. doi: 10.3390/ijms161126063.
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.
白细胞介素-33（IL-33）是白细胞介素-1家族细胞因子的新成员，由不同类型的免疫细胞和非免疫细胞表达。IL-33在细胞核中组成性表达，在那里它可以作为一种转录调节因子。到目前为止，尚未确定核IL-33的直接靶点，IL-33核功能的调节在很大程度上仍不清楚。在此，我们报告2型炎症细胞因子白细胞介素-13（IL-13）的转录受到核IL-33的正调控。IL-33可以直接结合到IL13基因座翻译起始位点之前的保守非编码序列（CNS）。此外，泛素特异性蛋白酶17（USP17）通过在K48和K63位点对IL-33进行去泛素化来调节IL-33的核功能和稳定性。我们的数据表明，核IL-33可以直接激活IL13基因转录，而去泛素酶USP17对其具有负调控作用。
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