title: STUB1 is essential for T-cell activation by ubiquitinating CARMA1.
abstract: Ag receptor engagement triggers lymphocyte activation and proliferation by activating several transcription factors including NF-κB. Caspase recruitment domain (CARD) containing membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) is an essential adaptor protein that links Ag receptors to NF-κB activation. Here, we identify stress-induced-phosphoprotein 1 homology and U-box containing protein 1 (STUB1) as a CARMA1-associated protein. STUB1 constitutively interacted with CARMA1, and the interaction was intensified by TCR stimulation. Downregulation of STUB1 expression by RNAi markedly diminished TCR-induced canonical NF-κB activation and IL-2 production. Furthermore, overexpression of STUB1 enhanced the ubiquitination of CARMA1, whereas knockdown of STUB1 abolished the endogenous ubiquitination of CARMA1 induced by TCR stimulation. Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys-27 linked, which is important for CARMA1-mediated NF-κB activation. These data provide the first evidence that ubiquitination of CARMA1 by STUB1 promotes TCR-induced NF-κB signaling.
authors: College of Life Sciences, Wuhan University, Wuhan, China.
authors: Shuai
authors: S
authors: Wang
authors: Yi
authors: Y
authors: Li
authors: Yun-Hong
authors: YH
authors: Hu
authors: Ren
authors: R
authors: Song
authors: Yan
authors: Y
authors: Gao
authors: Hai-Yun
authors: HY
authors: Liu
authors: Hong-Bing
authors: HB
authors: Shu
authors: Yu
authors: Y
authors: Liu
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D002384:Catalysis; D002460:Cell Line; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D053468:CARD Signaling Adaptor Proteins; D007376:Interleukin-2; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases; C426242:CARD11 protein, human; D006162:Guanylate Cyclase