CARMA1-BCL10-MALT1 complex (CBM complex) and Nuclear factor kappa B signaling pathway (NF-κB pathway) (CBM/NF-κB)

The CARMA1-BCL10-MALT1 (CBM) complex is a critical molecular signalosome that bridges antigen receptor signaling in T and B cells to the activation of the Nuclear factor kappa B (NF-κB) pathway (UniProt Q9BXL7, O95999, Q9UDY8). Upon stimulation of the T-cell or B-cell receptor, CARD11 (CARMA1) undergoes a conformational change that allows for the recruitment of BCL10 and MALT1, forming a large filamentous complex (PubMed: 20303873). This assembly triggers the activation of the IκB kinase (IKK) complex, leading to the phosphorylation and degradation of IκB proteins, which subsequently allows NF-κB to translocate into the nucleus and initiate the transcription of genes involved in cell survival, proliferation, and immune responses (PubMed: 19022946). Dysregulation of the CBM complex, often through gain-of-function mutations in CARD11 or chromosomal translocations involving MALT1 and BCL10, is a hallmark of several lymphoid malignancies, particularly activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) and MALT lymphoma (PubMed: 21307341). Consequently, components of the CBM complex, especially the proteolytic activity of MALT1, have emerged as promising therapeutic targets for the development of small-molecule inhibitors aimed at treating refractory lymphomas and autoimmune disorders (PubMed: 33853845).

Other names

CBM signalosomeCARD11-BCL10-MALT1 complexNF-kappaB signaling pathwayCARMA1-BCL10-MALT1 complex

Inhibition of MALT1 proteolytic activity, disruption of CBM complex assembly, and inhibition of IKK complex activation to prevent NF-κB nuclear translocation.