CARD11-BCL10-MALT1 signalosome complex (CBM complex)

The CARD11-BCL10-MALT1 signalosome complex (CBM complex) is a supramolecular assembly that functions as a critical signal transduction platform in lymphocytes. It bridges antigen receptor activation (via T-cell and B-cell receptors) to canonical NF-κB and JNK pathway activation. Upon receptor engagement, CARD11/CARMA1 undergoes phosphorylation-induced conformational changes, recruiting BCL10-MALT1 heterodimers. BCL10 oligomerizes into filaments, serving as a scaffold for further assembly. MALT1 binds directly to BCL10 and also acts as a scaffold and active protease, cleaving substrates such as CYLD and A20 to modulate immune signaling. The assembled CBM complex orchestrates the recruitment of downstream mediators, including E3 ubiquitin ligases (TRAF6) and kinases (TAK1, IKK complex), leading to NF-κB activation, which is essential for lymphocyte survival, proliferation, and adaptive immunity. Dysregulation or mutation within any CBM component can result in immunodeficiencies, lymphomas, and autoimmune disorders, making it a significant therapeutic target in immunology and cancer research.

Other names

CARD11/CARMA1-BCL10-MALT1 complexCARMA1/Bcl10/MALT1 signalosomeCBM complex

Inhibition of MALT1 protease activity (e.g., MALT1 inhibitors block downstream NF-κB signaling); Modulation of complex assembly, preventing downstream signaling; Disruption of CARD11-BCL10 interaction blocks signal transduction