Abstract
The homeobox gene GBX2 was identified as a target gene of the v-Myb oncoprotein encoded by the avian myeloblastosis virus (AMV). GBX2 activation by c-Myb requires signal transduction emanating from the cell surface while the leukemogenic AMV v-Myb constitutively induces the GBX2 gene. Mutations in the DNA binding domain of AMV-Myb render it independent of signaling events and concomitantly abrogate the collaboration between Myb and CCAAT Enhancer Binding Proteins (C/EBP), which are involved in granulocyte differentiation. Ectopic expression of GBX2 in growth factor-dependent myeloblasts induces monocytic features and independence from exogenous cytokines, reflecting distinct features of AMV-transformed cells. Our results suggest that Myb or factors it interacts with contribute to hematopoietic lineage choice and differentiation in a signal transduction-dependent fashion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autocrine Communication / physiology*
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Avian Proteins*
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Bone Marrow Cells / chemistry
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Bone Marrow Cells / physiology
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Cell Differentiation / genetics
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Chickens
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Cytokines
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DNA-Binding Proteins / physiology
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Gene Expression Regulation, Developmental / physiology
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Growth Substances / genetics
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Growth Substances / metabolism
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Hematopoiesis / genetics
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Hematopoietic Stem Cells / chemistry
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Hematopoietic Stem Cells / physiology
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism*
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Intercellular Signaling Peptides and Proteins*
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Molecular Sequence Data
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Monocytes / cytology*
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Oncogenes / physiology*
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Phenotype
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Promoter Regions, Genetic / physiology
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Signal Transduction / genetics
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Transformation, Genetic
Substances
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Avian Proteins
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Cytokines
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DNA-Binding Proteins
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Growth Substances
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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MGF protein, chicken