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A CARD10-dependent tonic signalosome activates MALT1 paracaspase and regulates IL-17/TNF-a driven keratinocyte inflammation

Israel, Laura and Bardet, Maureen and Huppertz, Antje and Mercado, Nicolas and Ginster, Stefanie and Unterreiner, Adeline and Schlierf, Anita and Goetschy, Jean Francois and Zerwes, Hans-Guenter and Roth, Lukas and Kolbinger, Frank and Bornancin, Frederic (2018) A CARD10-dependent tonic signalosome activates MALT1 paracaspase and regulates IL-17/TNF-a driven keratinocyte inflammation. Journal of investigative dermatology: Symposium proceedings.. ISSN 1529-1774; 1087-0024

Abstract

The paracaspase MALT1 (Mucosa associated lymphoid tissue lymphoma translocation protein 1) controls signaling downstream of several cell surface receptors, such as C-type lectin receptors on myeloid cells and antigen receptors on lymphocytes. Upon receptor engagement, MALT1, BCL10 (B-cell lymphoma/leukemia 10) and a CARD (Caspase recruitment domain) family member assemble into a ‘CBM’ complex, which is required to trigger MALT1 paracaspase activity and downstream transcriptional activation mechanisms (Meininger and Krappmann 2016; Rosebeck et al. 2011). Here, we found that CARD10 is highly expressed in proliferating keratinocytes and is responsible for a tonic level of paracaspase activity, driven by MALT1 isoform A. Furthermore, using the potent and selective MALT1 inhibitor MLT-827 (Bardet et al. 2018; Unterreiner et al. 2017), we reveal that MALT1 activity regulates pro-inflammatory responses downstream of IL-17/TNF-α.

Item Type: Article
Date Deposited: 26 May 2018 00:45
Last Modified: 26 May 2018 00:45
URI: https://oak.novartis.com/id/eprint/33789

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