USP22 is a positive regulator of NFATc2 on promoting IL2 expression.

Yayi Gao, Fang Lin, Peng Xu, Jia Nie, Zuojia Chen, Jinsong Su, Jiayou Tang, Qingsi Wu, Yangyang Li, Zhixiang Guo, Zhimei Gao, Dan Li, Jijia Shen, Shenglin Ge, Andy Tsun, Bin Li

FEBS letters 2014 Mar 18

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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. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Citation

Yayi Gao, Fang Lin, Peng Xu, Jia Nie, Zuojia Chen, Jinsong Su, Jiayou Tang, Qingsi Wu, Yangyang Li, Zhixiang Guo, Zhimei Gao, Dan Li, Jijia Shen, Shenglin Ge, Andy Tsun, Bin Li. USP22 is a positive regulator of NFATc2 on promoting IL2 expression. FEBS letters. 2014 Mar 18;588(6):878-83