Abstract
MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint upstream of the promoter of a novel gene, Bcl10. Bcl10 is a cellular homolog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD) homologous to that found in several apoptotic molecules. Bcl10 and E10 activated NF-kappaB but caused apoptosis of 293 cells. Bcl10 expressed in a MALT lymphoma exhibited a frameshift mutation resulting in truncation distal to the CARD. Truncated Bcl10 activated NF-kappaB but did not induce apoptosis. Wild-type Bcl10 suppressed transformation, whereas mutant forms had lost this activity and displayed gain-of-function transforming activity. Similar mutations were detected in other tumor types, indicating that Bcl10 may be commonly involved in the pathogenesis of human malignancy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Apoptosis
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B-Cell CLL-Lymphoma 10 Protein
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Base Sequence
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COS Cells
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Cell Line, Transformed
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Cell Transformation, Neoplastic
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Chromosomes, Human, Pair 1*
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Chromosomes, Human, Pair 14*
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Cloning, Molecular
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Gene Expression
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HeLa Cells
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Humans
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Lymphoma, B-Cell, Marginal Zone / genetics*
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Mice
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Molecular Sequence Data
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Mutation*
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NF-kappa B / metabolism
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / physiology
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Neoplasms / genetics
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Sequence Homology, Amino Acid
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Translocation, Genetic*
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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Bcl10 protein, mouse
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NF-kappa B
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Neoplasm Proteins
Associated data
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GENBANK/AJ006288
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GENBANK/AJ006289
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GENBANK/AJ006290
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GENBANK/AJ006410