title: The proteolytic activity of the paracaspase MALT1 is key in T cell activation.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Fabien
authors.initials: F
authors.lastname: Rebeaud
authors.forename: Stephan
authors.initials: S
authors.lastname: Hailfinger
authors.forename: Anita
authors.initials: A
authors.lastname: Posevitz-Fejfar
authors.forename: Myriam
authors.initials: M
authors.lastname: Tapernoux
authors.forename: Roger
authors.initials: R
authors.lastname: Moser
authors.forename: Daniel
authors.initials: D
authors.lastname: Rueda
authors.forename: Olivier
authors.initials: O
authors.lastname: Gaide
authors.forename: Montserrat
authors.initials: M
authors.lastname: Guzzardi
authors.forename: Emanuela M
authors.initials: EM
authors.lastname: Iancu
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fasel
authors.forename: Margot
authors.initials: M
authors.lastname: Thome
mesh_terms: 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*
chemical_list: 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