USP2a positively regulates TCR-induced NF-κB activation by bridging MALT1-TRAF6

doi:10.1007/s13238-012-2120-8

Prot Cell

2013, Vol. 4

Issue (1) : 62-70 https://doi.org/10.1007/s13238-012-2120-8 PMID: 23264041

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USP2a positively regulates TCR-induced NF-κB activation by bridging MALT1-TRAF6

Yi Li, Xiao He, Shuai Wang, Hong-Bing Shu, Yu Liu(

)

College of Life Sciences, Wuhan University, Wuhan 430072, China

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Abstract

The paracaspase MALT1 is essential for the activation of NF-κB in response to T cell receptor (TCR) stimulation. It recruits downstream TRAF6 and activates the E3 ligase activity of TRAF6 to polyubiquitinate several targets, which ultimately leads to NF-κB activation. Here we identified ubiquitin-specific protease 2a (USP2a) as a MALT1-associated protein by biochemical affinity purification. Endogenous USP2a constitutively interacted with TRAF6, but dynamically interacted with MALT1 and CARMA1 in a stimulation-dependent manner. RNA interference (RNAi)-mediated silencing of USP2a attenuated TCR-induced NF-κB activation and production of interleukin-2 (IL-2). In addition, the ubiquitination of MALT1 and TRAF6 were both suppressed by USP2a knockdown. By knockdown and reconstitution assays, we found that USP2a mediated the interaction between MALT1 and TRAF6 in a catalytic activity- dependent manner. Furthermore, USP2a deSUMOylated TRAF6. Our findings implicate that USP2a plays an important role in TCR signaling by deSUMOylating TRAF6 and mediating TRAF6-MALT1 interaction.

Keywords USP2a MALT1 TRAF6 T cell activation NF-κB

Corresponding Author(s): Liu Yu,Email:yuliu@whu.edu.cn

Issue Date: 01 January 2013

Cite this article:

Yi Li,Xiao He,Shuai Wang, et al. USP2a positively regulates TCR-induced NF-κB activation by bridging MALT1-TRAF6[J]. Prot Cell, 2013, 4(1): 62-70.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-012-2120-8
https://academic.hep.com.cn/pac/EN/Y2013/V4/I1/62

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