4i1p
From Proteopedia
Human MALT1 (caspase-IG3) in complex with activity based-probe
Structural highlights
Disease[MALT1_HUMAN] Note=A chromosomal aberration involving MALT1 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with BIRC2. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma. Function[MALT1_HUMAN] Enhances BCL10-induced activation of NF-kappa-B. Involved in nuclear export of BCL10. Binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity. Has ubiquitin ligase activity. MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion.[1] [2] [3] Publication Abstract from PubMedMALT1 paracaspase is activated upon antigen receptor stimulation to promote lymphocyte activation. In addition, deregulated MALT1 protease activity drives survival of distinct lymphomas such as the activated B cell type of diffuse large B cell lymphoma (ABC-DLBCL). Here, we designed fluorophore or biotin-coupled activity based-probes (ABP) that covalently modify the active center of MALT1. MALT1-ABPs are exclusively labeling an active modified full length form of MALT1 upon T cell stimulation. Further, despite the CARMA1 requirement for initial MALT1 activation, the MALT1-ABPs show that protease activity is not confined to the high-molecular CARMA1-BCL10-MALT1 (CBM) complex. Using biotin-coupled ABPs, we developed a robust assay for sensitive and selective detection of active MALT1 in cell lines, primary lymphocytes, and DLBCL tumor biopsies. Taken together, MALT1-ABPs represent powerful chemical tools to measure cellular MALT1 activation, determine efficacy of small molecule inhibitors, and classify lymphomas based on MALT1 activity status. Activity-Based Probes for Detection of Active MALT1 Paracaspase in Immune Cells and Lymphomas.,Eitelhuber AC, Vosyka O, Nagel D, Bognar M, Lenze D, Lammens K, Schlauderer F, Hlahla D, Hopfner KP, Lenz G, Hummel M, Verhelst SH, Krappmann D Chem Biol. 2014 Dec 30. pii: S1074-5521(14)00420-7. doi:, 10.1016/j.chembiol.2014.10.021. PMID:25556945[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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