title: Smurf1 represses TNF-α production through ubiquitination and destabilization of USP5.
abstract: Ubiquitin-specific peptidase 5 (USP5) has been demonstrated to be critical for the production of Tumor Necrosis Factor-alpha (TNF-α), a pivotal mediator for inflammatory responses. Besides, USP5 regulates p53 activation and DNA repair. However, the mechanism underlying the regulation of USP5, especially its responsible E3 ligase is still unclear. Here we found that Smad ubiquitination regulatory factor 1 (Smurf1) down regulated protein expression of USP5, and the E3 enzyme activity of Smurf1 was required for this function. We also revealed that Smurf1 interacted with USP5 and mediated its degradation via the ubiquitin proteasome pathway. Consequently, Smurf1 inhibited the production of TNF-α through down-regulation of USP5. Taken together, our study for the first time clarified that the E3 ligase Smurf1 regulates USP5 protein stability and USP5-mediated TNF-α production through the ubiquitin proteasome pathway.
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China; Institutes of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, 215003, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Qian
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Yukang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China. Electronic address: eygjgk@163.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu Province, 215123, China. Electronic address: huizheng@suda.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D015536:Down-Regulation / Q000502:physiology; D010450:Endopeptidases / Q000378:metabolism*; D004795:Enzyme Stability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; C091939:ubiquitin isopeptidase
keywords: E3 ligase; Proteasomal degradation; Protein ubiquitination; Smurf1; USP5