title: MALT1 protease: a new therapeutic target in B lymphoma and beyond?
abstract: The identification of mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) as a gene that is perturbed in the B-cell neoplasm MALT lymphoma, already more than a decade ago, was the starting point for an intense area of research. The fascination with MALT1 was fueled further by the observation that it contains a domain homologous to the catalytic domain of caspases and thus, potentially, could function as a protease. Discoveries since then initially revealed that MALT1 is a key adaptor molecule in antigen receptor signaling to the transcription factor NF-κB, which is crucial for lymphocyte function. However, recent discoveries show that this function of MALT1 is not restricted to lymphocytes, witnessed by the ever-increasing list of receptors from cells within and outside of the immune system that require MALT1 for NF-κB activation. Yet, a role for MALT1 protease activity was shown only recently in immune signaling, and its importance was then further strengthened by the dependency of NF-κB-addicted B-cell lymphomas on this proteolytic activity. Therapeutic targeting of MALT1 protease activity might, therefore, become a useful approach for the treatment of these lymphomas and, additionally, an effective strategy for treating other neoplastic and inflammatory disorders associated with deregulated NF-κB signaling.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA. lindaluc@umich.edu
authors.forename: Linda M
authors.initials: LM
authors.lastname: McAllister-Lucas
authors.forename: Mathijs
authors.initials: M
authors.lastname: Baens
authors.forename: Peter C
authors.initials: PC
authors.lastname: Lucas
mesh_terms: D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000379:methods; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: D061945:Caspase Inhibitors; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein