USP2a positively regulates TCR-induced NF-κB activation by bridging MALT1-TRAF6
Protein & Cell
; (12): 62-70, 2013.
Article
in En
| WPRIM
| ID: wpr-757833
Responsible library:
WPRO
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.
Full text:
1
Index:
WPRIM
Main subject:
Endopeptidases
/
Receptors, Antigen, T-Cell
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Signal Transduction
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NF-kappa B
/
Interleukin-2
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Jurkat Cells
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Caspases
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TNF Receptor-Associated Factor 6
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Gene Knockdown Techniques
/
HEK293 Cells
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Protein & Cell
Year:
2013
Type:
Article