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

Autor:	Eitelhuber AC; Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany., Vosyka O; Lehrstuhl für Chemie der Biopolymere, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising, Germany., Nagel D; Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany., Bognar M; Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany., Lenze D; Department of Pathology, Charité - University Medicine Berlin, Hindenburgdamm 30, 12200 Berlin, Germany., Lammens K; Department of Biochemistry, Gene Center, Ludwig-Maximilian University, Feodor-Lynen-Strasse 25, 81377 Munich, Germany., Schlauderer F; Department of Biochemistry, Gene Center, Ludwig-Maximilian University, Feodor-Lynen-Strasse 25, 81377 Munich, Germany., Hlahla D; Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany., Hopfner KP; Department of Biochemistry, Gene Center, Ludwig-Maximilian University, Feodor-Lynen-Strasse 25, 81377 Munich, Germany., Lenz G; Department of Medicine A, Translational Oncology, Albert-Schweitzer Campus 1, University Hospital Muenster, 48149 Muenster, Germany., Hummel M; Department of Pathology, Charité - University Medicine Berlin, Hindenburgdamm 30, 12200 Berlin, Germany., Verhelst SH; Lehrstuhl für Chemie der Biopolymere, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising, Germany., Krappmann D; Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany. Electronic address: daniel.krappmann@helmholtz-muenchen.de.
Jazyk:	angličtina
Zdroj:	Chemistry & biology [Chem Biol] 2015 Jan 22; Vol. 22 (1), pp. 129-38. Date of Electronic Publication: 2014 Dec 31.
DOI:	10.1016/j.chembiol.2014.10.021
Abstrakt:	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. (Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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