title: Targeting MALT1 Proteolytic Activity in Immunity, Inflammation and Disease: Good or Bad?
abstract: MALT1 is a signaling protein that plays a key role in immunity, inflammation, and lymphoid malignancies. For a long time MALT1 was believed to function as a scaffold protein, providing an assembly platform for other signaling proteins. This view changed dramatically when MALT1 was also found to have proteolytic activity and a capacity to fine-tune immune responses. Preclinical studies have fostered the belief that MALT1 is a promising therapeutic target in autoimmunity and B cell lymphomas. However, recent studies have shown that mice expressing catalytically-inactive MALT1 develop multi-organ inflammation and autoimmunity, and thus have tempered this initial enthusiasm. We discuss recent findings, highlighting the urgent need for a better mechanistic and functional understanding of MALT1 in host defense and disease.
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Demeyer
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Jens
authors.initials: J
authors.lastname: Staal
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium. Electronic address: rudi.beyaert@irc.vib-ugent.be.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D061945:Caspase Inhibitors / Q000494:pharmacology*; D020169:Caspases / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D061945:Caspase Inhibitors; D016328:NF-kappa B; D009363:Neoplasm Proteins; D020169:Caspases; C400109:MALT1 protein, human; C498509:Malt1 protein, mouse; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
keywords: MALT1; inflammation; lymphocytes; lymphoma; protease; therapeutic targeting