Proposed model for MALT1 function in NFKB activation

Proposed model for MALT1 function in NF-κB activation. B-cell receptor (BCR) stimulation induces formation of the CBM complex, which controls NF-κB activation through at least two different mechanisms. The scaffold function of BCL10 and MALT1 are required for TRAF6 recruitment and ubiquitination-dependent activation of the IKK complex, which phosphorylates IκB proteins. The protease activity of MALT1 also contributes to NF-κB activation in an IKK-independent manner, through cleavage of an unknown substrate (???). This might control IκBβ degradation, which occurs with slower kinetics than IκBα degradation and is sustained (), possibly because it depends on additional signaling events. Alternatively, MALT1 protease activity might control NF-κB1 activation at the level of its nuclear translocation or transcriptional activity. The presence of oncogenic mutations in CARMA1 or its upstream regulators may render this pathway constitutively active in diffuse large B-cell lymphoma of the activated B-cell type (ABC DLBCL) (see text for details).

Publication

Antigen Receptor Signaling to NF-κB via CARMA1, BCL10, and MALT1. (2010) Margot Thome, et al. Cold Spring Harb Perspect Biol. 2010 Sep;2(9):a003004. Figure: F4. All organisms Danio rerio Homo sapiens

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