Activity-Based Probes for Detection of Active MALT1 Paracaspase in Immune Cells and Lymphomas

作者：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 H L; Krappmann Daniel^*

来源：Chemistry & Biology, 2015, 22(1): 129-138.

DOI：10.1016/j.chembiol.2014.10.021

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.

• 出版日期2015-1-22