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Open Access Green as soon as Postprint is submitted to ZB.
Activity-based probes for detection of active MALT1 paracaspase in immune cells and lymphomas.
Chem. Biol. 22, 129-138 (2014)
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
Journal
Chemistry and Biology
Quellenangaben
Volume: 22,
Issue: 1,
Pages: 129-138
Publisher
Elsevier
Publishing Place
Cambridge
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOXI)
Institute of Molecular Toxicology and Pharmacology (TOXI)