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Open Access Green as soon as Postprint is submitted to ZB.
Malt1 ubiquitination triggers NF-kB signaling upon T-cell activation.
EMBO J. 26, 4634-4645 (2007)
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 IkB kinase (IKK)/NF-kB 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-kB 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-kB pathway.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Malt1; NF-kB; regulatory ubiquitination; T-cell signaling
ISSN (print) / ISBN
0261-4189
e-ISSN
1460-2075
Journal
EMBO Journal, The
Quellenangaben
Volume: 26,
Issue: 22,
Pages: 4634-4645
Publisher
Wiley
Publishing Place
Heidelberg, Germany
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Signaling and Translation (SAT)