| Literature DB >> 25070893 |
Lei Han1, Jing Yang2, Xiuwen Wang1, Qingsi Wu3, Shuying Yin2, Zhiyuan Li2, Jing Zhang2, Yue Xing2, Zuojia Chen2, Andy Tsun1, Dan Li1, Miranda Piccioni1, Yu Zhang4, Qiang Guo5, Lindi Jiang6, Liming Bao7, Ling Lv8, Bin Li9.
Abstract
Stable retinoic acid-related orphan nuclear receptor γt (RORγt) expression is pivotal for the development and function of Th17 cells. Here we demonstrate that expression of the transcription factor RORγt can be regulated through deubiquitination, which prevents proteasome-mediated degradation. We establish that USP17 stabilizes RORγt protein expression by reducing RORγt polyubiquitination at its Lys-360 residue. In contrast, knockdown of endogenous USP17 in Th17 cells resulted in decreased RORγt protein levels and down-regulation of Th17-related genes. Furthermore, USP17 expression was up-regulated in CD4(+) T cells from systemic lupus erythematosus patients. Our data reveal a molecular mechanism in which RORγt expression in Th17 cells can be positively regulated by USP17, thereby modulating Th17 cell functions.Entities:
Keywords: Autoimmune Disease; Deubiquitination; RORγt; Systemic Lupus Erythematosus; T Cell Biology; Th17 Cells; Transcription Factor; USP17; Ubiquitin-dependent Protease
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Year: 2014 PMID： 25070893 PMCID： PMC4162160 DOI： 10.1074/jbc.M114.565291
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157