The paracaspase MALT1: biological function and potential for therapeutic inhibition.
The paracaspase MALT1 has a central role in the activation of lymphocytes and other immune cells including myeloid cells, mast cells and NK cells. MALT1 activity is required not only for the immune response, but also for the development of natural Treg cells that keep the immune response in check. Exaggerated MALT1 activity has been associated with the development of lymphoid malignancies, and recently developed MALT1 inhibitors show promising anti-tumor effects in xenograft models of diffuse large B cell lymphoma. In this review, we provide an overview of the present understanding of MALT1's function, and discuss possibilities for its therapeutic targeting based on recently developed inhibitors and animal models.
Department of Biochemistry, University of Lausanne, 1066, Epalinges, Switzerland.
Maike
M
Jaworski
Department of Biochemistry, University of Lausanne, 1066, Epalinges, Switzerland. margot.thomemiazza@unil.ch.
Margot
M
Thome
D020816:Amino Acid Motifs; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008958:Models, Molecular; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology
D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D020169:Caspases; C400109:MALT1 protein, human; C498509:Malt1 protein, mouse; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
Autoimmunity; Lymphoma; NF-κB; Protease; Regulatory T cells