Figure 1.

The waves of MALT1 activation. MALT1 is recruited into CARD/BCL10/MALT1 (CBM) complexes after stimulation of antigen receptors or under chronic stimulatory conditions resulting from mutations in signaling components of the pathway, for example, gain-of-function (GoF) mutations in CARD11. CBM assembly triggers MALT1 paracaspase activity. MALT1 cleaves several substrates including BCL10. MALT1 can also auto-cleave, particularly at R149,⁸ which is promoted by TRAF6.⁹ This process represents a feed-forward mechanism that releases a highly functional MALT1 species. MALT1 auto proteolysis, and cleavage of BCL10 by MALT1 may contribute to downregulation of the pathway.⁹