USP22 通过促进 IL2 表达正向调控 NFATc2。
USP22 is a positive regulator of NFATc2 on promoting IL2 expression.
机构信息
Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
出版信息
FEBS Lett. 2014 Mar 18;588(6):878-83. doi: 10.1016/j.febslet.2014.02.016. Epub 2014 Feb 20.
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 function.
激活 T 细胞核因子（NFAT）是 T 细胞激活的重要调节因子。然而，NFATc2 调节 IL2 转录的分子机制尚不完全清楚。在这项研究中，我们表明，泛素特异性蛋白酶 22（USP22），作为一种癌症干细胞标志物，特异性地与 NFATc2 相互作用并使其去泛素化。USP22 稳定了 NFATc2 蛋白水平，这需要其去泛素酶活性。与这些观察结果一致，在 T 细胞中耗尽 USP22 会降低细胞因子 IL2 的表达，IL2 是标志 T 效应细胞激活的细胞因子。因此，我们的发现揭示了 NFATc2 的一个以前未被描述的正向调节因子，表明靶向 USP22 的去泛素酶活性可能具有治疗益处，以控制 IL2 表达和 T 细胞功能。
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