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 on coprotein encoded by the avian myeloblastosis virus (AMV). GBX2 activa tion by c-Myb requires signal transduction emanating from the cell sur face while the leukemogenic AMV v-Myb constitutively induces the GBX2 gene. Mutations in the DHA binding domain of AMV-Myb render it indepen dent of signaling events and concomitantly abrogate the collaboration between Myb and CCAAT Enhancer Binding Proteins (C/EBP), which are inv olved in granulocyte differentiation. Ectopic expression of GBX2 in gr owth factor-dependent myeloblasts induces monocytic features and indep endence from exogenous cytokines, reflecting distinct features of AMV- transformed cells. Our results suggest that Myb or factors it interact s with contribute to hematopoietic lineage choice and differentiation in a signal transduction-dependent fashion.