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Graß, C. ; Ober, F. ; Sixt, C. ; Nemati Moud, B. ; Antoshkina, I. ; Eberstadt, F. ; Puhach, A.* ; Avar, G. ; Keßler, A. ; O'Neill, T.J. ; Seeholzer, T. ; Kranich, J.* ; Brocker, T.* ; Lammens, K.* ; Menden, M.P. ; Zielinski, C.E.* ; Krappmann, D.

LUBAC modulates CBM complex functions downstream of TRAF6 in T cells.

Nat. Commun. 16:9899 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The CARD11-BCL10-MALT1 (CBM) complex drives NF-κB signaling and MALT1 protease activation after T cell receptor (TCR) stimulation, forming a central signaling hub in adaptive immunity. Both linear ubiquitin chain assembly complex (LUBAC), consisting of HOIP, HOIL-1 and SHARPIN, and TRAF6 interact with the CBM complex. Still, the coordinated activity of these E3 ligases in controlling CBM activity remains elusive. Here we demonstrate that LUBAC, unlike TRAF6, is largely dispensable for TCR-induced NF-κB activation in human CD4+ T cells. However, HOIP contributes to NF-κB target gene expression and, with TRAF6, modulates MALT1 substrate recognition, influencing T cell responses. Further, LUBAC-mediated conjugation of Met1-linked ubiquitin chains to BCL10 strictly depends on TRAF6, but putative Met1-ubiquitin acceptor lysines in BCL10 serve essential structural roles that limit accessibility within BCL10-MALT1 filaments. Thus, LUBAC acts downstream of TRAF6 to modulate MALT1 substrate recognition and to catalyze BCL10 ubiquitination, which is incompatible with BCL10-MALT1 filament formation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Nf-kappa-b; Chain Assembly Complex; Ubiquitin Chains; Malt1 Cleaves; Activation; Receptor; Bcl10; Recognition; Lymphoma; Nemo
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 16, Issue: 1, Pages: , Article Number: 9899 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Institute of Computational Biology (ICB)
Grants Deutsche Krebshilfe (German Cancer Aid)
Deutsche Forschungsgemeinschaft (German Research Foundation)