USP22 is a positive regulator of NFATc2 on promoting IL2 expression
USP22 is a positive regulator of NFATc2 on promoting IL2 expression
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USP22 是 NFATc2 促进 IL2 表达的正调节因子
DOI：
10.1016/j.febslet.2014.02.016
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发表时间：
2014-03-18
期刊：
影响因子：
3.5
通讯作者：
Li, Bin
中科院分区：
文献类型：
--
作者：
Gao, Yayi;Lin, Fang;Li, Bin
活化T细胞核因子（NFAT）是T细胞活化的重要调节因子。然而，NFATc2调控IL2转录的分子机制尚不完全清楚。在这项研究中，我们发现泛素特异性蛋白酶22 (USP22)，被称为癌症干细胞标志物，特异性地与NFATc2相互作用并去泛素化。USP22稳定了NFATc2蛋白水平，这需要它的去泛素酶活性。与这些观察结果一致，T细胞中USP22的缺失降低了IL2的表达，IL2是一种标志T效应细胞激活的细胞因子。因此，我们的研究结果揭示了一种以前未被发现的NFATc2阳性调节因子，表明靶向USP22的去泛素酶活性可能对控制il - 2表达和T细胞功能具有治疗益处。蛋白相互作用的结构总结：NFATc2通过抗标签共免疫沉淀与USP22物理相互作用（1,2）(C) 2014 Federation of European Biochemical Societies。Elsevier b.v.版权所有。
Nuclear factor of activated T cells (NFAT) is an important regulator of T cell activation. However, the molecular mechanism whereby NFATc2 regulates IL2 transcription is not fully understood. In this study, we showed that ubiquitin-specific protease 22 (USP22), known as a cancer stem cell marker, specifically interacted with and deubiquitinated NFATc2. USP22 stabilized NFATc2 protein levels, which required its deubiquitinase activity. Consistent with these observations, depletion of USP22 in T cells reduced the expression of IL2, which is a cytokine that signifies T effector cell activation. Our findings thus unveil a previously uncharacterized positive regulator of NFATc2, suggesting that targeting the deubiquitinase activity of USP22 could have therapeutic benefit to control IL2 expression and T cell functionStructured summary of protein interactions:NFATc2 physically interacts with USP22 by anti tag coimmunoprecipitation (1, 2) (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.