title: Targeting B-cell lymphomas with inhibitors of the MALT1 paracaspase.
abstract: The paracaspase MALT1 is an Arg-specific protease that cleaves multiple substrates to promote lymphocyte proliferation and survival. The catalytic activity of MALT1 is normally tightly regulated by antigen receptor triggering, which promotes MALT1 activation by its inducible monoubiquitination-dependent dimerization. Constitutive MALT1 activity is a hallmark of specific subsets of B-cell lymphomas, which are characterized by chromosomal translocations or point mutations that activate MALT1 or its upstream regulators. Recent findings suggest that such lymphomas may be sensitive to treatment with MALT1 inhibitors. Here we review recent progress in the understanding of MALT1 function and regulation, and the development of small molecule MALT1 inhibitors for therapeutic applications.
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hailfinger
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.affiliation: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland. Electronic address: margot.thomemiazza@unil.ch.
authors.forename: Margot
authors.initials: M
authors.lastname: Thome
mesh_terms: D000818:Animals; D020169:Caspases; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000201:enzymology; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein