Malt1 ubiquitination triggers NF‐κB signaling upon T‐cell activation
A Oeckinghaus, E Wegener, V Welteke, U Ferch… - The EMBO …, 2007 - embopress.org
A Oeckinghaus, E Wegener, V Welteke, U Ferch, SÇ Arslan, J Ruland, C Scheidereit…
The EMBO journal, 2007•embopress.orgTriggering 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 IκB kinase
(IKK)/NF‐κB 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 …
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 IκB kinase
(IKK)/NF‐κB 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 …
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 IκB kinase (IKK)/NF‐κB 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/IKKγ. 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‐κB 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‐κB pathway.
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