The proteolytic activity of the paracaspase MALT1 is key in T cell activation
- 10 February 2008
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 9 (3) , 272-281
- https://doi.org/10.1038/ni1568
Abstract
The paracaspase MALT1 is pivotal in antigen receptor–mediated lymphocyte activation and lymphomagenesis. MALT1 contains a caspase-like domain, but it is unknown whether this domain is proteolytically active. Here we report that MALT1 had arginine-directed proteolytic activity that was activated after T cell stimulation, and we identify the signaling protein Bcl-10 as a MALT1 substrate. Processing of Bcl-10 after Arg228 was required for T cell receptor–induced cell adhesion to fibronectin. In contrast, MALT1 activity but not Bcl-10 cleavage was essential for optimal activation of transcription factor NF-κB and production of interleukin 2. Thus, the proteolytic activity of MALT1 is central to T cell activation, which suggests a possible target for the development of immunomodulatory or anticancer drugs.Keywords
This publication has 47 references indexed in Scilit:
- Are metacaspases caspases?The Journal of cell biology, 2007
- Malt1 ubiquitination triggers NF-κB signaling upon T-cell activationThe EMBO Journal, 2007
- Leishmania major metacaspase can replace yeast metacaspase in programmed cell death and has arginine-specific cysteine peptidase activityInternational Journal for Parasitology, 2007
- Negative feedback loop in T cell activation through IκB kinase-induced phosphorylation and degradation of Bcl10Proceedings of the National Academy of Sciences, 2007
- Serpin1 of Arabidopsis thaliana is a Suicide Inhibitor for Metacaspase 9Journal of Molecular Biology, 2006
- Constitutive NF-κB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activityCancer Cell, 2005
- Bcl10 activates the NF-κB pathway through ubiquitination of NEMONature, 2003
- Requirement for CARMA1 in Antigen Receptor-Induced NF-κB Activation and Lymphocyte ProliferationCurrent Biology, 2003
- Carma1, a CARD‐containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF‐κB activation1FEBS Letters, 2001
- CARD11 and CARD14 Are Novel Caspase Recruitment Domain (CARD)/Membrane-associated Guanylate Kinase (MAGUK) Family Members that Interact with BCL10 and Activate NF-κBJournal of Biological Chemistry, 2001