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| Item Type: | Article |
|---|---|
| Title: | Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation |
| Creators Name: | Oeckinghaus, A., Wegener, E., Welteke, V., Ferch, U., Coel Arslan, S., Ruland, J., Scheidereit, C. and Krappmann, D. |
| Abstract: | Triggering of antigen receptors on lymphocytes is critical for initiating adaptive immune response against pathogens. T-cell receptor (TCR) engagement induces the formation of the Carma1-Bcl10-Malt1 (CBM) complex that is essential for activation of the IkappaB kinase (IKK)/NF-kappaB pathway. However, the molecular mechanisms that link CBM complex formation to IKK activation remain unclear. Here we report that Malt1 is polyubiquitinated upon T-cell activation. Ubiquitin chains on Malt1 provide a docking surface for the recruitment of the IKK regulatory subunit NEMO/IKKgamma. TRAF6 associates with Malt1 in response to T-cell activation and can function as an E3 ligase for Malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of Malt1. Multiple lysine residues in the C-terminus of Malt1 serve as acceptor sites for the assembly of polyubiquitin chains. Malt1 mutants that lack C-terminal ubiquitin acceptor lysines are impaired in rescuing NF-kappaB signaling and IL-2 production in Malt1-/- T cells. Thus, our data demonstrate that induced Malt1 ubiquitination is critical for the engagement of CBM and IKK complexes, thereby directing TCR signals to the canonical NF-kappaB pathway. |
| Keywords: | Malt1, NFkappa-B, Regulatory Ubiquitination, T-Cell Signaling |
| Source: | EMBO Journal |
| ISSN: | 0261-4189 |
| Publisher: | Nature Publishing Group |
| Volume: | 26 |
| Number: | 22 |
| Page Range: | 4634-4645 |
| Date: | 14 November 2007 |
| Additional Information: | The original publication is available at http://npg.nature.com/ |
| Official Publication: | https://doi.org/10.1038/sj.emboj.7601897 |
| PubMed: | View item in PubMed |
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