ArticleProceedings of the National Academy of Sciences of the United States of America2018
Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 76 citations in OpenAlex.
- MALT1 alternative splicing-A molecular rheostat for balancing immune activation and homeostasis.Science advances · 2026Article
- A role for the protease MALT1 in EBV-mediated B-cell transformation by Latent Membrane Proteins 1 and 2.Leukemia · 2026Article
- A histidine switch controls the pH-responsive self-assembly of a helical protein filament.bioRxiv : the preprint server for biology · 2026Article
- BLM regulates MALT1-driven NF-κB signalling and is targetable in B-cell malignancies.Cell death & disease · 2026Article
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Mechanistic Insights Into Immune Cell Dysregulation Mediated by Novel Heterozygous Variants in CARD11 and MALT1.Journal of clinical immunology · 2026Article
- Therapeutic targeting of MALT1 in oncology: Mechanism, inhibitor development, and clinical prospects.Journal of cell communication and signaling · 2026Review
- LUBAC modulates CBM complex functions downstream of TRAF6 in T cells.Nature communications · 2025Article
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- A histidine switch regulates pH-dependent filament formation by the caspase-9 CARD.bioRxiv : the preprint server for biology · 2025Article
- Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells.The Journal of experimental medicine · 2025Article
- A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma.The Journal of clinical investigation · 2025Article
- Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels.The Biochemical journal · 2025Review
- Downregulation of A20 Expression Related to T Cells by Staphylococcal Enterotoxin A Treatment.Bulletin of experimental biology and medicine · 2025Article
- A structural atlas of death domain fold proteins reveals their versatile roles in biology and function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A new-disease-causing dominant-negative variant in CARD11 gene in a Chinese case with recurrent fever.Scientific reports · 2024Article
- ABIN1 is a negative regulator of effector functions in cytotoxic T cells.EMBO reports · 2024Article
- Liquid-liquid phase separation in diseases.MedComm · 2024Review
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- Response to Bruton's tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy.Cancer cell · 2024Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination. Here we present cryo-electron microscopy (cryo-EM) structure of the BCL10 CARD filament at 4.0-Å resolution. The structure redefines CARD-CARD interactions compared with the previous EM structure determined from a negatively stained sample. Surprisingly, time-lapse confocal imaging shows that BCL10 polymerizes in a unidirectional manner. CARMA1, the BCL10 nucleator, serves as a hub for formation of star-shaped filamentous networks of BCL10 and significantly decreases the lag period of BCL10 polymerization. Cooperative MALT1 interaction with BCL10 filaments observed under EM suggests immediate dimerization of MALT1 in the BCL10 filamentous scaffold. In addition, TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies, likely resulting in all-or-none activation of the downstream pathway. Collectively, these data reveal biophysical mechanisms in the assembly of the CARMA1-BCL10-MALT1-TRAF6 complex for signal transduction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.