USP38 critically promotes asthmatic pathogenesis by stabilizing JunB protein.
USP38 critically promotes asthmatic pathogenesis by stabilizing JunB protein.
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USP38 通过稳定 JunB 蛋白来显着促进哮喘发病机制。
DOI：
10.1084/jem.20172026
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发表时间：
2018-11-05
期刊：
影响因子：
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通讯作者：
Qian Y
中科院分区：
文献类型：
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作者：
Chen S;Yun F;Yao Y;Cao M;Zhang Y;Wang J;Song X;Qian Y
虽然最近在一项GWAS研究中报道了usp38位于与人类哮喘相关的染色体位点，但其潜在的病理作用仍然未知。Chen等人现在证明了usp38在哮喘发病机制中是必不可少的。USP38由TCR信号诱导，进而促进JunB稳定，特异性调节Th2细胞分化。Th2免疫反应在过敏性哮喘发病机制中起关键作用。调控Th2免疫的分子机制尚不清楚。在这里，我们报道泛素特异性蛋白酶USP38对th2介导的过敏性哮喘至关重要。TCR刺激上调USP38水平，而USP38反过来介导JunB （Th2发育特异性转录因子）的蛋白稳定。因此，在体外和体内，USP38是tcr诱导的Th2细胞因子产生和Th2发育的特异性需要，并且USP38缺陷小鼠对OVA或HDM诱导的哮喘发病机制具有抗性。在机制上，USP38直接与JunB相关，去泛素化lys -48连接的JunB多泛素化，从而阻断tcr诱导的JunB周转。USP38是第一个被发现的去泛素酶，专门用于Th2免疫和相关的哮喘。
Although usp38 has recently been reported to be in a chromosome locus associated with human asthma in a GWAS study, its potential pathological role remains unknown. Chen et al. now demonstrate that usp38 is essential for asthmatic pathogenesis. USP38 is induced by TCR signaling and in turn promotes JunB stabilization to specifically regulate Th2 cell differentiation. Th2 immune response is critical for allergic asthma pathogenesis. Molecular mechanisms for regulating Th2 immunity are still not well understood. Here we report that the ubiquitin-specific protease USP38 is crucial for Th2-mediated allergic asthma. TCR stimulation up-regulated the USP38 level, and USP38 in turn mediated the protein stabilization of JunB, a transcription factor specific for Th2 development. Consequently, USP38 was specifically required for TCR-induced production of Th2 cytokines and Th2 development both in vitro and in vivo, and USP38-deficient mice were resistant to asthma pathogenesis induced by OVA or HDM. Mechanistically, USP38 directly associated with JunB, deubiquitinated Lys-48–linked poly-ubiquitination of JunB, and consequently blocked TCR-induced JunB turnover. USP38 represents the first identified deubiquitinase specifically for Th2 immunity and the associated asthma.
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影响因子：
44.1
作者：
Hu H;Sun SC
通讯作者：
Sun SC
DOI：
10.1084/jem.20151426
发表时间：
2016-03-07
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Hu H;Wang H;Xiao Y;Jin J;Chang JH;Zou Q;Xie X;Cheng X;Sun SC
通讯作者：
Sun SC
影响因子：
32.4
作者：
Oliver, Paula M.;Cao, Xiao;Yang, Baoli
通讯作者：
Yang, Baoli
DOI：
10.1084/jem.20122327
发表时间：
2013-07-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu X;Li H;Zhong B;Blonska M;Gorjestani S;Yan M;Tian Q;Zhang DE;Lin X;Dong C
通讯作者：
Dong C
影响因子：
30.8
作者：
通讯作者：
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