Article abstract
Nature Immunology 9, 272 - 281 (2008)
Published online: 10 February 2008 | doi:10.1038/ni1568
The proteolytic activity of the paracaspase MALT1 is key in T cell activation
Fabien Rebeaud1,4, Stephan Hailfinger1,4, Anita Posevitz-Fejfar1, Myriam Tapernoux1, Roger Moser1, Daniel Rueda1, Olivier Gaide1,3, Montserrat Guzzardi1, Emanuela M Iancu2, Nathalie Rufer2, Nicolas Fasel1 & Margot Thome1
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-
B 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.
- Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
- Multidisciplinary Oncology Center, Lausanne University Hospital, CH-1005 Lausanne, Switzerland.
- Present address: University Medical Center, CH-1211 Geneva 4, Switzerland.
- These authors contributed equally to this work.
Correspondence to: Margot Thome1 e-mail: margot.thomemiazza@unil.ch
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