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

Authors :: Gao Y
Lin F
Xu P
Nie J
Chen Z
Su J
Tang J
Wu Q
Li Y
Guo Z
Gao Z
Li D
Shen J
Ge S
Tsun A
Li B
Source :: FEBS letters [FEBS Lett] 2014 Mar 18; Vol. 588 (6), pp. 878-83. Date of Electronic Publication: 2014 Feb 20.
Publication Year :: 2014
Abstract: 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.<br /> (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)