1. MALT1 activation by TRAF6 needs neither BCL10 nor CARD11.
- Author
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Bardet, Maureen, Seeholzer, Thomas, Unterreiner, Adeline, Woods, Simone, Krappmann, Daniel, and Bornancin, Frédéric
- Subjects
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LYMPHOID tissue , *ANTIGEN receptors , *BCL genes , *UBIQUITINATION , *OLIGOMERIZATION , *PROTEOLYTIC enzymes - Abstract
Abstract The MALT1 (Mucosa associated lymphoid tissue lymphoma translocation protein 1) paracaspase couples antigen receptors on lymphocytes to downstream signaling events. Activation of MALT1 is known to involve stimulus-dependent CBM complex formation, that is, the recruitment of BCL10-bound MALT1 to a CARD-Coiled Coil protein. Beyond this canonical, CBM-dependent mechanism of MALT1 activation, recent studies suggest that MALT1 protease activity may be triggered by alternative mechanisms. For instance, the E3-ligase TRAF6 can activate MALT1 proteolytic function and induce MALT1 auto-cleavage. However, the interplay between CBM and TRAF6 with regard to MALT1 activation has remained incompletely elucidated. Here, by generating CRISPR/Cas9-derived knock-out Jurkat T-cells, we show that TRAF6 was dispensable for CARD11/BCL10-dependent MALT1 activation upon T-cell stimulation. However, ectopically-expressed TRAF6 could induce MALT1 activity in Jurkat T-cells devoid of either CARD11 or BCL10. These data provide unequivocal evidence that TRAF6-mediated MALT1 activation does not require the upstream scaffold CARD11 or the interaction between MALT1 and BCL10. Thus, TRAF6 may be part of a previously unidentified non-canonical pathway that triggers MALT1 protease activity independently of canonical CBM signalosomes. Highlights • TRAF6 is not strictly required for MALT1 activation downstream of CARD11/BCL10. • TRAF6 can activate MALT1 independently of CARD11 or BCL10. • MALT1 oligomerization is involved in its activation by TRAF6. • Pathways leading to TRAF6 oligomerization may broaden the range of MALT1 activation mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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