Cooperative transformation by MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins generated by the variant t(1;19) in acute lymphoblastic leukemia.
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.
Prima
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Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610-3633, USA. vprima@ufl.edu
Hunger
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D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion; D048430:Cell Shape; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics / Q000648:ultrastructure; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006801:Humans; D026161:MADS Domain Proteins / Q000235:genetics*; D064326:MEF2 Transcription Factors; D051379:Mice; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D041681:NIH 3T3 Cells; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014161:Transduction, Genetic; D014178:Translocation, Genetic; D014410:Tumor Stem Cell Assay
D016895:Culture Media, Serum-Free; C412481:DAZAP1 protein, human; C500965:DAZAP1-MEF2D fusion protein, human; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human; C500964:MEF2D-DAZAP1 fusion protein, human; D018006:Myogenic Regulatory Factors; D015514:Oncogene Proteins, Fusion; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins