Abstract
Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas are characterized genetically by the t(11;18)(q21;q21) translocation, which yields chimeric transcripts encoding structurally distinct API2/MALT1 fusion proteins. In this study, we provide functional evidence for the contribution of API2/MALT1 fusion proteins to transformation of cells in culture by activating the NF-kappaB pathway through a RelB/p50 dimer. Using microchip gene expression analysis, we demonstrate that different forms of the API2/MALT1 proteins activate both unique and overlapping gene programs in cells. In addition to this genome reprogramming, expression of distinct API2/MALT1 fusion products inhibits DNA damage-induced, p53-mediated apoptosis in an NF-kappaB-dependent manner. Collectively, these data reveal previously unknown functional diversity among API2/MALT1 fusion products and their function in NF-kappaB signaling as it connects to the apoptotic program, a pathway with strong relevance to cancer. Furthermore, they provide evidence underlying the emerging role of the NF-kappaB signaling pathway in the inhibition of apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / physiology
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Apoptosis / radiation effects
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Cell Line
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Dimerization
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Humans
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Lymphoma, B-Cell, Marginal Zone / metabolism*
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Lymphoma, B-Cell, Marginal Zone / pathology
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Mice
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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NIH 3T3 Cells
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism*
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transcription Factor RelB
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic
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Transfection
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Tumor Suppressor Protein p53 / antagonists & inhibitors*
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Tumor Suppressor Protein p53 / physiology
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Ultraviolet Rays
Substances
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API2-MALT1 fusion protein, human
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NF-kappa B
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Nuclear Proteins
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins
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RELB protein, human
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Recombinant Proteins
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Relb protein, mouse
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Transcription Factors
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Transcription Factor RelB