title: T-cell receptor-induced JNK activation requires proteolytic inactivation of CYLD by MALT1.
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.
authors: Department of Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Zwijnaarde, Ghent, Belgium.
authors: Jens
authors: J
authors: Staal
authors: Yasmine
authors: Y
authors: Driege
authors: Tine
authors: T
authors: Bekaert
authors: Annelies
authors: A
authors: Demeyer
authors: David
authors: D
authors: Muyllaert
authors: Petra
authors: P
authors: Van Damme
authors: Kris
authors: K
authors: Gevaert
authors: Rudi
authors: R
authors: Beyaert
mesh_terms: D020169:Caspases / Q000378:metabolism*; D002853:Chromatography, Liquid; D017931:DNA Primers / Q000235:genetics; D000074749:Deubiquitinating Enzyme CYLD; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology* / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D053719:Tandem Mass Spectrometry; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D025521:Tumor Suppressor Proteins; D048670:MAP Kinase Kinase 4; D010447:Peptide Hydrolases; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein