title: USP2a positively regulates TCR-induced NF-κB activation by bridging MALT1-TRAF6.
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.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
mesh_terms: D020169:Caspases / Q000378:metabolism*; D010450:Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase
chemical_list: D007376:Interleukin-2; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D048029:TNF Receptor-Associated Factor 6; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein