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

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
JournalProtein and Cell
Volume4
Issue number1
DOIs
StatePublished - 2013

Keywords

  • MALT1
  • NF-κB
  • T cell activation
  • TRAF6
  • USP2a

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

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