Title: Activity-Based Probes for Detection of Active MALT1 Paracaspase in Immune Cells and Lymphomas
Authors: Eitelhuber, Andrea C
Vosyka, Oliver
Nagel, Daniel
Bognar, Miriam
Lenze, Dido
Lammens, Katja
Schlauderer, Florian
Hlahla, Daniela
Hopfner, Karl-Peter
Lenz, Georg
Hummel, Michael
Verhelst, Steven
Krappmann, Daniel # ×
Issue Date: Jan-2015
Publisher: Current Biology Ltd.
Series Title: Chemistry & Biology vol:22 issue:1 pages:129-38
Article number: 10.1016/j.chembiol.2014.10.021
Abstract: MALT1 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.
ISSN: 1074-5521
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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