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Title: T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-kappaB inhibitor A20
Authors: Coornaert, Beatrice *
Baens, Thijs *
Heyninck, Karen
Bekaert, Tine
Haegman, Mira
Staal, Jens
Sun, Lijun
Chen, Zhijian J
Marynen, Peter
Beyaert, Rudi # ×
Issue Date: Jan-2008
Publisher: Nature America Inc.
Series Title: Nature immunology vol:9 issue:3 pages:263-271
Abstract: The paracaspase MALT1 mediates T cell antigen receptor-induced signaling to the transcription factor NF-kappaB and is indispensable for T cell activation and proliferation. Enhanced expression of MALT1 or aberrant expression of a fusion protein of the apoptosis inhibitor API2 and MALT1 has been linked to mucosa-associated lymphoid tissue lymphoma. Despite the presence of a caspase-like domain, MALT1 proteolytic activity has not yet been demonstrated. Here we show that T cell antigen receptor stimulation induced recruitment of the NF-kappaB inhibitor A20 into a complex of MALT1 and the adaptor protein Bcl-10, leading to MALT1-mediated processing of A20. API2-MALT1 expression likewise resulted in cleavage of A20. MALT1 cleaved human A20 after arginine 439 and impaired its NF-kappaB-inhibitory function. Our studies identify A20 as a substrate of MALT1 and emphasize the importance of MALT1 proteolytic activity in the 'fine tuning' of T cell antigen receptor signaling.
URI: 
ISSN: 1529-2908
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Human Genome Laboratory
Department of Human Genetics - miscellaneous
* (joint) first author
× corresponding author
# (joint) last author

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