TitleMolecular pathways: targeting MALT1 paracaspase activity in lymphoma.
Publication TypeJournal Article
Year of Publication2013
AuthorsFontan, Lorena, and Melnick Ari
JournalClin Cancer Res
Date Published2013 Dec 15
KeywordsAdaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, B-Cell CLL-Lymphoma 10 Protein, CARD Signaling Adaptor Proteins, Caspases, Guanylate Cyclase, Humans, Lymphoma, Large B-Cell, Diffuse, Molecular Targeted Therapy, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein, Neoplasm Proteins, NF-kappa B, Receptors, Antigen, Receptors, Antigen, T-Cell, Signal Transduction

<p>MALT1 mediates the activation of NF-κB in response to antigen receptor signaling. MALT1, in association with BCL10 and CARD11, functions as a scaffolding protein to activate the inhibitor of IκB kinase (IKK) complex. In addition, MALT1 is a paracaspase that targets key proteins in a feedback loop mediating termination of the NF-κB response, thus promoting activation of NF-κB signaling. Activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL), which tend to be more resistant to chemotherapy, are often biologically dependent on MALT1 activity. Newly developed MALT1 small-molecule inhibitors suppress the growth of ABC-DLBCLs in vitro and in vivo. This review highlights the recent advances in the normal and disease-related functions of MALT1. Furthermore, recent progress targeting MALT1 proteolytic activity raises the possibility of deploying MALT1 inhibitors for the treatment of B-cell lymphomas and perhaps autoimmune diseases that involve increased B- or T-cell receptor signaling.</p>

Alternate JournalClin Cancer Res
PubMed ID24004675