The proteolytic activity of the paracaspase MALT1 is key in T cell activation.
The paracaspase MALT1 is pivotal in antigen receptor-mediated lymphocyte activation and lymphomagenesis. MALT1 contains a caspase-like domain, but it is unknown whether this domain is proteolytically active. Here we report that MALT1 had arginine-directed proteolytic activity that was activated after T cell stimulation, and we identify the signaling protein Bcl-10 as a MALT1 substrate. Processing of Bcl-10 after Arg228 was required for T cell receptor-induced cell adhesion to fibronectin. In contrast, MALT1 activity but not Bcl-10 cleavage was essential for optimal activation of transcription factor NF-kappaB and production of interleukin 2. Thus, the proteolytic activity of MALT1 is central to T cell activation, which suggests a possible target for the development of immunomodulatory or anticancer drugs.
Rebeaud
Fabien
F
Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
Hailfinger
Stephan
S
Posevitz-Fejfar
Anita
A
Tapernoux
Myriam
M
Moser
Roger
R
Rueda
Daniel
D
Gaide
Olivier
O
Guzzardi
Montserrat
M
Iancu
Emanuela M
EM
Rufer
Nathalie
N
Fasel
Nicolas
N
Thome
Margot
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000074018:B-Cell CLL-Lymphoma 10 Protein; D020169:Caspases / Q000502:physiology*; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D010447:Peptide Hydrolases; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein