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| Subject Categories: Signal Transduction | Immunology |
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| The EMBO Journal
(2007) 26, 4634–4645, doi:10.1038/sj.emboj.7601897 Published online 18 October 2007 |
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Malt1 ubiquitination triggers NF- B signaling upon T-cell activation |
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| Andrea Oeckinghaus1, 2, 3, Elmar Wegener1, Verena Welteke1, Uta Ferch4, Seda Çöl Arslan2, Jürgen Ruland4, Claus Scheidereit2 and Daniel Krappmann1 |
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1 GSF—National Research Center for Environment and Health, Institute of Toxicology, Neuherberg, Germany 2 Max-Delbrück—Center for Molecular Medicine, Berlin, Germany 3 Faculty of Biology, Chemistry and Pharmacy, Free University Berlin, Germany 4 Third Medical Department, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany To whom correspondence should be addressed Daniel Krappmann, GSF—National Research Center for Environment and Health, Institute of Toxicology, Ingolstädter Landstrasse 1, Neuherberg 85764, Germany. Tel.: +49 89 3187 3461; Fax: +49 89 3187 3449; E-mail: Daniel.Krappmann@gsf.de Received 17 July 2007; Accepted 26 September 2007; Published online 18 October 2007. |
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| Abstract |
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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 IB kinase (IKK)/NF-B 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/IKK . 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-B 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-B pathway. |
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| Keywords: Malt1, NF-B, regulatory ubiquitination, T-cell signaling |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSE2 enzymes: expanding the 'ubi-verse' of immune signaling Nature Immunology News and Views (01 Sep 2006) Nature Immunology News and Views (01 Mar 2008) RESEARCHMalt1 ubiquitination triggers NF-κB signaling upon T-cell activation The EMBO Journal Article |
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