title: The protease activity of the paracaspase MALT1 is controlled by monoubiquitination.
abstract: The protease activity of the paracaspase MALT1 is central to lymphocyte activation and lymphomagenesis, but how this activity is controlled remains unknown. Here we identify a monoubiquitination of MALT1 on Lys644 that activated the protease function of MALT1. Monoubiquitinated MALT1 had enhanced protease activity, whereas a ubiquitination-deficient MALT1 mutant with replacement of that lysine with arginine (MALT1(K644R)) had less protease activity, which correlated with impaired induction of interleukin 2 (IL-2) via the T cell antigen receptor in activated T cells. Expression of MALT1(K644R) diminished the survival of cells derived from diffuse large B cell lymphoma of the activated B cell-like subtype (ABC DLBCL), which require constitutive protease activity of MALT1 for survival. Thus, monoubiquitination of MALT1 is essential for its catalytic activation and is therefore a potential target for the treatment of ABC-DLBCL and for immunomodulation.
authors: Department of Biochemistry, Center of Immunity and Infection, University of Lausanne, Epalinges, Switzerland.
authors: Christiane
authors: C
authors: Pelzer
authors: Katrin
authors: K
authors: Cabalzar
authors: Annette
authors: A
authors: Wolf
authors: Montserrat
authors: M
authors: Gonzalez
authors: Georg
authors: G
authors: Lenz
authors: Margot
authors: M
authors: Thome
mesh_terms: D019943:Amino Acid Substitution; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000378:metabolism; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D013601:T-Lymphocytes / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; D025801:Ubiquitin; D010447:Peptide Hydrolases; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein