Genomes and Genes
Role of RNA-Binding Proteins in BCR/ABL Leukemogenesis
Principal Investigator: D Perrotti
Affiliation: The Ohio State University
Abstract: Shuttling hnRNPs control the fate of eukaryotic mRNAs throughout their journey from the active site of transcription to that of translation; thus, gain or loss of their function in hematopoietic cells might result in altered hematopoiesis and/or emergence of leukemia. In BCR/ABL-expressing cells, there is a marked increase in the levels of different RNA binding proteins including FUS, hnRNP A1, hnRNP E2 and hnRNP K, four shuttling hnRNPs involved in the regulation of mRNA biogenesis, processing, nuclear export, and translation. Ectopic expression and/or inhibition of the activity of FUS, hnRNP A1 and hnRNP E2 affects the proliferation, survival, and differentiation of normal and BCR/ABL-expressing cells, suggesting that enhanced expression/activity of certain RNA-binding proteins plays an important but as yet unrecognized role in BCR/ABL leukemogenesis. Thus, the objective of this proposal is: 1) To investigate the mechanisms regulating hnRNP E2 and hnRNP A1 expression/function in BCR/ABL-expressing cells. 2) To identify hnRNP A1 and hnRNP E2-associated mRNAs encoding proteins differentially expressed in CML-blast crisis and CML-chronic phase cells. 3) To determine the BCR/ABL-dependent mechanisms regulating the expression/function of hnRNP K and determine whether hnRNP K function(s) is(are) required for BCR/ABL-induced leukemogenesis.
Funding Period: 2003-08-15 - 2007-07-31
more information: NIH RePORT
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The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
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Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
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Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210 2207, USA
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Department of Molecular Virology, Immunology, and Medical Genetics, Human Cancer Genetics Program, The Ohio State University, Columbus, OH 43210, USA
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Human Cancer Genetics Program, Department Molecular Virology Immunology and Medical Genetics
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Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
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School of Biomedical Sciences, University of Newcastle, Callaghan, New South Wales, Australia
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Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 41230, USA
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Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA
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Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, 460 West 12th Ave, Columbus, OH 43210, USA
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Division of Hematology Oncology, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
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Human Cancer Genetics Program, Depatment of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center and Center for RNA Biology, The Ohio State University, Columbus, OH 43210 2207, USA
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Department of Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
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Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA
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Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
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Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA
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Human Cancer Genetics Program, The Ohio State University Medical Center, Columbus, OH 43240, USA
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Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, 233 South and 10th Street, Philadelphia, PA 19107, USA
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Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
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Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
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The Molecular Biology and Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43240, USA
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Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA
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Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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