Abstract
Bcl10 and MALT1, products of distinct chromosomal translocations in mucosa-associated lymphoid tissue lymphoma, cooperate in activating NF-kappaB. Mice lacking Bcl10 demonstrate severe immunodeficiency associated with failure of lymphocytes to activate nuclear factor kappaB (NF-kappaB) in response to antigen receptor stimulation and protein kinase C activation. We characterize Bimp1, a new signaling protein that binds Bcl10 and activates NF-kappaB. Bimp1-mediated NF-kappaB activation requires Bcl10 and IkappaB kinases, indicating that Bimp1 acts upstream of these mediators. Bimp1, Bcl10, and MALT1 form a ternary complex, with Bcl10 bridging the Bimp1/MALT1 interaction. A dominant negative Bimp1 mutant inhibits NF-kappaB activation by anti-CD3 ligation, phorbol ester, and protein kinase C expression. These results suggest that Bimp1 links surface receptor stimulation and protein kinase C activation to Bcl10/MALT1, thus leading to NF-kappaB induction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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B-Cell CLL-Lymphoma 10 Protein
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Caspases
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DNA, Complementary / analysis
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Enzyme Activation
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Guanylate Kinases
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Humans
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I-kappa B Kinase
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Lymphoma, B-Cell, Marginal Zone*
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Molecular Sequence Data
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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NF-kappa B / biosynthesis*
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Neoplasm Proteins / metabolism
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Neoplasm Proteins / physiology*
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Nucleoside-Phosphate Kinase / physiology*
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Protein Kinase C / physiology*
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Protein Serine-Threonine Kinases / physiology
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, human
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DNA, Complementary
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NF-kappa B
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Neoplasm Proteins
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Protein Serine-Threonine Kinases
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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Protein Kinase C
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Nucleoside-Phosphate Kinase
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Guanylate Kinases
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Caspases
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MALT1 protein, human
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
Associated data
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GENBANK/AF363456
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GENBANK/AF363457