STUB1 is essential for T-cell activation by ubiquitinating CARMA1

Shuai Wang, Yi Li, Yun Hong Hu, Ren Song, Yan Gao, Hai Yun Liu, Hong Bing Shu, Yu Liu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1034-1041
Number of pages8
JournalEuropean Journal of Immunology
Volume43
Issue number4
DOIs
StatePublished - Apr 1 2013

Keywords

  • CARMA1
  • NF-κB pathway
  • STUB1
  • Signal transduction
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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