Deubiquitination and stabilization of T-bet by USP10
Deubiquitination and stabilization of T-bet by USP10
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USP10 对 T-bet 的去泛素化和稳定化。
DOI：
10.1016/j.bbrc.2014.05.037
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发表时间：
2014-07-04
影响因子：
3.1
通讯作者：
Shi, Guochao
中科院分区：
文献类型：
--
作者：
Pan, Lina;Chen, Zuojia;Shi, Guochao
T-box转录因子T-bet在Th1细胞的发育、分化和功能中起着关键作用。它主要通过促进Th1标志细胞因子ifn - γ的表达来驱动Th1免疫反应。尽管发现T-bet与许多免疫介导的疾病（如哮喘和系统性硬化症）有关，但对T-bet稳定性和功能的调节知之甚少。在这里，我们发现USP10，一个羧基端泛素加工蛋白酶，可以与细胞核中的T-bet相互作用。过表达USP10直接抑制T-bet泛素化，增加T-bet的表达。我们进一步证实了槲皮素（一种已知的T-bet抑制剂）可以靶向USP10。槲皮素处理以蛋白酶体依赖的方式下调USP10并促进T-bet降解。此外，我们发现USP10在哮喘患者PBMC中表达上调，表明USP10可能维持高水平的T-bet和ifn - γ对抗th2主导的炎症。(C) 2014爱思唯尔公司版权所有。
The T-box transcriptional factor T-bet is crucial in the development, differentiation and function of Th1 cells. It drives Th1 immune response primarily through promoting expression of Th1 hallmark cytokine IFN-gamma. Although T-bet was found associated with many immune-mediated diseases such as asthma and systemic sclerosis, little is known about the regulation of T-bet stability and function. Here we identified USP10, a carboxyl-terminal ubiquitin-processing protease, could interact with T-bet in the nucleus. Overexpression of USP10 directly inhibited T-bet ubiquitination and increased the expression of T-bet. We further confirmed Quercetin, a reported inhibitor of T-bet, could target USP10. Quercetin treatment downregulated USP10 and promoted T-bet degradation in a proteasome dependent way. Moreover, we found USP10 expression was upregulated in asthmatic patient PBMC, suggesting USP10 may maintain high level of T-bet and IFN-gamma to fight against Th2-dominated inflammation. (C) 2014 Elsevier Inc. All rights reserved.