COP9 signalosome controls the Carma1-Bcl10-Malt1 complex upon T-cell stimulation.
The Carma1-Bcl10-Malt1 (CBM) complex connects T-cell receptor (TCR) signalling to the canonical IkappaB kinase (IKK)/NF (nuclear factor)-kappaB pathway. Earlier studies have indicated that the COP9 signalosome (CSN), a pleiotropic regulator of the ubiquitin/26S proteasome system, controls antigen responses in T cells. The CSN is required for the degradation of the NF-kappaB inhibitor IkappaBalpha, but other molecular targets involved in T-cell signalling remained elusive. Here, we identify the CSN subunit 5 (CSN5) as a new interactor of Malt1 and Carma1. T-cell activation triggers the recruitment of the CSN to the CBM complex, and CSN downregulation impairs TCR-induced IKK activation. Furthermore, the CSN is required for maintaining the stability of Bcl10 in response to T-cell activation. Taken together, our data provide evidence for a functional link between the evolutionarily conserved CSN and the adaptive immunoregulatory CBM complex in T cells.
Welteke
Verena
V
Department Cellular Signal Integration, Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Toxicology, Ingolstädter Landstrasse 1, Neuherberg 85764, Germany.
Eitelhuber
Andrea
A
Düwel
Michael
M
Schweitzer
Katrin
K
Naumann
Michael
M
Krappmann
Daniel
D
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D000075686:COP9 Signalosome Complex; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D046912:Multiprotein Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D051550:I-kappa B Kinase; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; C426242:CARD11 protein, human; D006162:Guanylate Cyclase