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Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation

Item Type:Article
Title:Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation
Creators Name:Oeckinghaus, A. and Wegener, E. and Welteke, V. and Ferch, U. and Coel Arslan, S. and Ruland, J. and 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 (U.S.A.)
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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