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Eitelhuber, A.C. ; Vosyka, O.* ; Nagel, D. ; Bognar, M. ; Lenze, D.* ; Lammens, K.* ; Schlauderer, F.* ; Hlahla, D. ; Hopfner, K.P.* ; Lenz, G.* ; Hummel, M.* ; Verhelst, S.H.* ; Krappmann, D.

Activity-based probes for detection of active MALT1 paracaspase in immune cells and lymphomas.

Chem. Biol. 22, 129-138 (2014)
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Nf-kappa-b; Protease Activity; Abc-dlbcl; T-cells; In-vivo; Activation; Cleavage; Phosphorylation; Identification; Inhibitors
ISSN (print) / ISBN 1074-5521
e-ISSN 1879-1301
Quellenangaben Volume: 22, Issue: 1, Pages: 129-138 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge
Reviewing status Peer reviewed