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Keywords:

Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Apoptosis, Base Sequence, COS Cells, Cell Line, Transformed, Cell Transformation, Neoplastic, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 14, Cloning, Molecular, Gene Expression, Hela Cells, Humans, Lymphoma, Mucosa-Associated Lymphoid Tissue, Mice, Molecular Sequence Data, Mutation, NF-kappa B, Neoplasm Proteins, Neoplasms, Research Support, Non-U.S. Gov't, Sequence Homology, Amino Acid, Translocation, Genetic, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, POLYMERASE CHAIN-REACTION, FOLLICULAR LYMPHOMA, TISSUE, GENE, TRANSFORMATION, P53, VISUALIZATION, ABNORMALITIES, ACTIVATION, APOPTOSIS, B-Cell CLL-Lymphoma 10 Protein, HeLa Cells, Lymphoma, B-Cell, Marginal Zone, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

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.