Abstract
NF-kappaB (Rel) transcription factors control physiological and pathological immune cell function. The scaffold proteins Bcl-10 and MALT1 couple antigen-receptor signals to the canonical NF-kappaB pathway and are pivotal in lymphomagenesis. Here we found that Bcl-10 and MALT1 differentially regulated B cell receptor-induced activation of RelA and c-Rel. Bcl-10 was essential for recruitment of the kinase IKK into lipid rafts for the activation of RelA and c-Rel, for blocking apoptosis and for inducing division after B cell receptor ligation. In contrast, MALT1 participated in survival signaling but was not involved in IKK recruitment or activation and was dispensable for RelA induction and proliferation. MALT1 selectively activated c-Rel to control a distinct subprogram. Our results provide mechanistic insights into B cell receptor-induced survival and proliferation signals and demonstrate the selective control of c-Rel in the canonical NF-kappaB pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Apoptosis / physiology
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B-Cell CLL-Lymphoma 10 Protein
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Caspases / immunology
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Caspases / metabolism*
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Cell Division / physiology
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Cell Survival / physiology
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Flow Cytometry
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Fluorescent Antibody Technique
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Immunoblotting
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Immunoprecipitation
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Lymphocyte Activation / immunology*
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Membrane Microdomains / metabolism
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Mice
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Mice, Transgenic
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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NF-kappa B / metabolism*
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Neoplasm Proteins / immunology
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Neoplasm Proteins / metabolism*
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Proto-Oncogene Proteins c-rel / metabolism*
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Receptors, Antigen, B-Cell / immunology
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Receptors, Antigen, B-Cell / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / immunology*
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Transcription Factor RelA / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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B-Cell CLL-Lymphoma 10 Protein
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Bcl10 protein, mouse
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NF-kappa B
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Neoplasm Proteins
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Proto-Oncogene Proteins c-rel
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Receptors, Antigen, B-Cell
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Rela protein, mouse
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Transcription Factor RelA
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Caspases
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Malt1 protein, mouse
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein