Abstract
The paracaspase mucosa-associated lymphoid tissue 1 (MALT1) is central to lymphocyte activation and lymphomagenesis. MALT1 mediates antigen receptor signalling to NF-κB by acting as a scaffold protein. Furthermore, MALT1 has proteolytic activity that contributes to optimal NF-κB activation by cleaving the NF-κB inhibitor A20. Whether MALT1 protease activity is involved in other signalling pathways, and the identity of the relevant substrates, is unknown. Here, we show that T-cell receptors (TCR) activation, as well as overexpression of the oncogenic API2-MALT1 fusion protein, results in proteolytic inactivation of CYLD by MALT1, which is specifically required for c-jun N-terminal kinase (JNK) activation and the inducible expression of a subset of genes. These results indicate a novel role for MALT1 proteolytic activity in TCR-induced JNK activation and reveal CYLD cleavage as the underlying mechanism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Caspases / metabolism*
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Chromatography, Liquid
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DNA Primers / genetics
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Deubiquitinating Enzyme CYLD
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Electrophoresis, Polyacrylamide Gel
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Enzyme Activation / physiology
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Enzyme-Linked Immunosorbent Assay
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Gene Expression Regulation / immunology*
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Gene Expression Regulation / physiology
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HEK293 Cells
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Humans
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Immunoblotting
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Jurkat Cells
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Lymphocyte Activation / physiology*
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MAP Kinase Kinase 4 / metabolism*
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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Neoplasm Proteins / metabolism*
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Peptide Hydrolases / metabolism
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Polymerase Chain Reaction
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction / physiology*
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Tandem Mass Spectrometry
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Tumor Suppressor Proteins / metabolism*
Substances
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DNA Primers
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Neoplasm Proteins
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Receptors, Antigen, T-Cell
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Tumor Suppressor Proteins
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MAP Kinase Kinase 4
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Peptide Hydrolases
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CYLD protein, human
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Deubiquitinating Enzyme CYLD
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Caspases
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MALT1 protein, human
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein