Journal Article

T-cell receptor-induced JNK activation requires proteolytic inactivation of CYLD by MALT1

Demeyer, Annelies, Van Damme, Petra, Staal, Jens, Muyllaert, David, Beyaert, Rudi, Driege, Yasmine, Gevaert, Kris, Bekaert, Tine

2011

Overview

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. Beyaert et al establish the paracaspase MALT1 as novel regulator of JNK signalling. Molecularly, MALT1 elicits this new activity by cleavage and inactivation of the deubiquitinase CylD downstream of T‐cell receptor activation. The paper thus expands the molecular functions of MALT1 from regulating NF‐κB signals to regulating JNK activity.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: AP-1 / Caspases - metabolism / Cellular biology / Chromatography, Liquid / cytokine / Deubiquitinating Enzyme CYLD / DNA Primers - genetics / Electrophoresis, Polyacrylamide Gel / EMBO19 / EMBO37 / Enzyme Activation - physiology / Enzyme-Linked Immunosorbent Assay / Gene Expression Regulation - immunology / Gene Expression Regulation - physiology / HEK293 Cells / Humans / Immune system / Immunoblotting / Inactivation / Jurkat Cells / Lymphocyte Activation - physiology / Lymphocytes / MAP kinase / MAP Kinase Kinase 4 - metabolism / Molecular biology / Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein / Neoplasm Proteins - metabolism / Peptide Hydrolases - metabolism / Polymerase Chain Reaction / Proteins / Receptors, Antigen, T-Cell - metabolism / Signal transduction / Signal Transduction - physiology / Tandem Mass Spectrometry / Tumor Suppressor Proteins - metabolism / ubiquitination