title: Probes to monitor activity of the paracaspase MALT1.
abstract: The human paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) plays a central role in nuclear factor-κB (NF-κB) signaling as both a protease and scaffolding protein. Knocking out MALT1 leads to impaired NF-κB signaling and failure to mount an effective immune response. However, it is unclear to which degree it is the scaffolding function versus the proteolytic activity of MALT1 that is essential. Previous work involving a MALT1 inhibitor with low selectivity suggests that the enzymatic function plays an important role in different cell lines. To help elucidate this proteolytic role of MALT1, we have designed activity-based probes that inhibit its proteolytic activity. The probes selectively label active enzyme and can be used to inhibit MALT1 and trace its activity profile, helping to create a better picture of the significance of the proteolytic function of MALT1.
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA; Graduate School of Biomedical Sciences, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Janna
authors.initials: J
authors.lastname: Hachmann
authors.affiliation: Cancer Biology Program, Stanford School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford School of Medicine, Stanford, CA 94305, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Edgington-Mitchell
authors.affiliation: Division of Bioorganic Chemistry, Wroclaw University of Technology, 50-370 Wroclaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Poreba
authors.affiliation: Department of Pathology, Stanford School of Medicine, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Sanman
authors.affiliation: Division of Bioorganic Chemistry, Wroclaw University of Technology, 50-370 Wroclaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Drag
authors.affiliation: Department of Pathology, Stanford School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bogyo
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA. Electronic address: gsalvesen@sanfordburnham.org.
authors.forename: Guy S
authors.initials: GS
authors.lastname: Salvesen
mesh_terms: D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection
chemical_list: D015335:Molecular Probes; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein