The homeobox gene GBX2, a target of the myb oncogene, mediates autocrine growth and monocyte differentiation.
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.
Kowenz-Leutz
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E
Max-Delbrück-Centrum for Molecular Medicine, Berlin, Germany.
Herr
P
P
Niss
K
K
Leutz
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A
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D030161:Avian Proteins; D001854:Bone Marrow Cells / Q000737:chemistry / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002645:Chickens; D016207:Cytokines; D004268:DNA-Binding Proteins / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology*; D009857:Oncogenes / Q000502:physiology*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014170:Transformation, Genetic
D030161:Avian Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C059626:MGF protein, chicken