2018/08/15 by J. Randall McAuley, Tanner J. Freeman, Prasanna Ekambaram +2 · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · Immunology and Microbiology · #NF-κB Signaling Pathways #Cytokine Signaling Pathways and Interactions #Immune Response and Inflammation #Biology #Receptor tyrosine kinase #Cell biology #Signal transduction #Cancer research #Scaffold protein #G protein-coupled receptor
paper · pdf · doi:10.3389/fimmu.2018.01887
openalex publication_date 2018/08/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
The CARMA-Bcl10-MALT1 (CBM) signalosome is an intracellular protein complex composed of a CARMA scaffolding protein, the Bcl10 linker protein, and the MALT1 protease. This complex was first recognized because the genes encoding its components are targeted by mutation and chromosomal translocation in lymphoid malignancy. We now know that the CBM signalosome plays a critical role in normal lymphocyte function by mediating antigen receptor-dependent activation of the pro-inflammatory, pro-survival NF-κB transcription factor, and that deregulation of this signaling complex promotes B-cell lymphomagenesis. More recently, we and others have demonstrated that a CBM signalosome also operates in cells outside of the immune system, including in several solid tumors. While CARMA1 (also referred to as CARD11) is expressed primarily within lymphoid tissues, the related scaffolding protein, CARMA3 (CARD10), is more widely expressed and participates in a CARMA3-containing CBM complex in a variety of cell types. The CARMA3-containing CBM complex operates downstream of specific G protein-coupled receptors (GPCRs) and/or growth factor receptor tyrosine kinases (RTKs). Since inappropriate expression and activation of GPCRs and/or RTKs underlies the pathogenesis of several solid tumors, there is now great interest in elucidating the contribution of CARMA3-mediated cellular signaling in these malignancies. Here, we summarize the key discoveries leading to our current understanding of the role of CARMA3 in solid tumor biology and highlight the current gaps in our knowledge.