Nuclear factor kappa-light-chain-enhancer of activated B cells signaling adaptor complex (NF-κB signaling adaptor complex) (NF-κB signaling adaptor complex)

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling adaptor complex, primarily represented by the CARMA1-BCL10-MALT1 (CBM) complex, is a critical multi-protein assembly that mediates signal transduction from various cell surface receptors to the NF-κB pathway (Ruland & Hartjes, 2019). Upon activation of antigen receptors on T and B cells, or specific G protein-coupled receptors, these adaptor proteins aggregate to form a high-molecular-weight signalosome (Juilland & Thome, 2018). This complex facilitates the recruitment and activation of the IκB kinase (IKK) complex, which subsequently phosphorylates IκBα, leading to its degradation and the nuclear translocation of NF-κB transcription factors (UniProt P60484). This pathway is essential for regulating genes involved in the innate and adaptive immune response, cell proliferation, and survival (PubMed: 30635667). Dysregulation of the CBM complex, such as constitutive activation through mutations in CARD11 (CARMA1) or MALT1, is a key driver in several lymphoid malignancies, including activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) (Frontiers in Oncology, 2020). Therapeutic strategies targeting this complex focus on inhibiting the proteolytic activity of MALT1 or preventing the assembly of the adaptor proteins (ClinicalTrials.gov: NCT03900715). While promising for treating cancer and autoimmune diseases, targeting these adaptors carries risks of systemic immunosuppression and increased susceptibility to opportunistic infections (Nature Reviews Drug Discovery, 2021).

Other names

CBM complexCARMA1-BCL10-MALT1 complexIKK complexSignalosomeIκB kinase complex

Inhibition of MALT1 protease activity, disruption of CBM complex assembly, and inhibition of IKK complex activation.