The proteolytic activity of the paracaspase MALT1 is key in T cell activation

• Published in: Nature immunology Vol. 9; no. 3; pp. 272 - 281
• Main Authors: Fasel, Nicolas, Rueda, Daniel, Moser, Roger, Rufer, Nathalie, Rebeaud, Fabien, Tapernoux, Myriam, Guzzardi, Montserrat, Iancu, Emanuela M, Thome, Margot, Gaide, Olivier, Hailfinger, Stephan, Posevitz-Fejfar, Anita
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2008; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adhesion; B-Cell CLL-Lymphoma 10 Protein; Biomedical and Life Sciences; Biomedicine; Caspases - physiology; Cell Line; Cellular proteins; Electrophoresis, Gel, Two-Dimensional; Humans; Immunology; Infectious Diseases; Jurkat Cells; Lymphocyte Activation - immunology; Lymphocytes; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; Neoplasm Proteins - physiology; NF-kappa B - metabolism; Peptide Hydrolases - metabolism; Physiological aspects; Protein Isoforms - metabolism; Proteolysis; T cells; T-Lymphocytes - immunology; Switzerland
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni1568

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-κB 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.