Abstract
A variant t(1;19)(q23;p13.3) translocation creates reciprocal DAZAP1/MEF2D and MEF2D/DAZAP1 fusion genes that are expressed in acute lymphoblastic leukemia. We used retroviral gene transfer to ectopically express wild-type and chimeric DAZAP1 and MEF2D fusion proteins in NIH 3T3 cells. In soft agar assays, each of the fusion proteins transformed 3T3 cells with a 20-fold increase in colony formation as compared to empty vector or native MEF2D or DAZAP1 proteins. Co-expression of both DAZAP1/MEF2D and MEF2D/DAZAP1 led to a threefold increase in colony formation as compared to either fusion protein alone. Expression of wild-type DAZAP1, MEF2D or DAZAP1/MEF2D allowed 3T3 cells to proliferate under low serum (0.5%) conditions and suppressed apoptosis. In contrast, MEF2D/DAZAP1 expression did not facilitate proliferation in low serum and led to a modest increase in apoptosis. Both MEF2D/DAZAP1 and DAZAP1/MEF2D have oncogenic properties, and co-expression of both fusion proteins is synergistic.
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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Cell Adhesion
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Cell Shape
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Cell Transformation, Neoplastic / genetics
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Chromosomes, Human, Pair 1 / genetics
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Chromosomes, Human, Pair 1 / ultrastructure
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Chromosomes, Human, Pair 19 / genetics
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Chromosomes, Human, Pair 19 / ultrastructure
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Culture Media, Serum-Free / pharmacology
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Humans
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MADS Domain Proteins / genetics*
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MEF2 Transcription Factors
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Mice
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Myogenic Regulatory Factors / genetics*
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NIH 3T3 Cells
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Oncogene Proteins, Fusion / biosynthesis
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / physiology*
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RNA-Binding Proteins / genetics*
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Recombinant Fusion Proteins / physiology
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Transduction, Genetic
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Translocation, Genetic
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Tumor Stem Cell Assay
Substances
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Culture Media, Serum-Free
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DAZAP1 protein, human
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DAZAP1-MEF2D fusion protein, human
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MADS Domain Proteins
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MEF2 Transcription Factors
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MEF2D protein, human
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MEF2D-DAZAP1 fusion protein, human
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Myogenic Regulatory Factors
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Oncogene Proteins, Fusion
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RNA-Binding Proteins
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Recombinant Fusion Proteins