T cell antigen receptor stimulation induces MALT1 paracaspase - Mediated cleavage of the NF-κB inhibitor A20

Beatrice Coornaert, Mathijs Baens, Karen Heyninck, Tine Bekaert, Mira Haegman, Jens Staal, Lijun Sun, Zhijian J. Chen, Peter Marynen, Rudi Beyaert

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283 Scopus citations

Abstract

The paracaspase MALT1 mediates T cell antigen receptor-induced signaling to the transcription factor NF-κB 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-κB 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-κB-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.

Original languageEnglish (US)
Pages (from-to)263-271
Number of pages9
JournalNature Immunology
Volume9
Issue number3
DOIs
StatePublished - Mar 2008

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ASJC Scopus subject areas

  • Immunology

Cite this

Coornaert, B., Baens, M., Heyninck, K., Bekaert, T., Haegman, M., Staal, J., Sun, L., Chen, Z. J., Marynen, P., & Beyaert, R. (2008). T cell antigen receptor stimulation induces MALT1 paracaspase - Mediated cleavage of the NF-κB inhibitor A20. Nature Immunology, 9(3), 263-271. https://doi.org/10.1038/ni1561