Oncoprotein v-Myb and Retinoic Acid Receptor α Are Mutual Antagonists

ABSTRACT: The process of hematopoiesis is critically dependent on correct interactions of multiple regulatory molecules and transcription factors. We have studied the interactions of the v-Myb and retinoic acid receptor proteins which have opposing effects on hematopoiesis. While v-mybacts as a transforming oncogene preventing differentiation of monoblasts to macrophages, RARα functions as an anti-oncogene arresting the growth of v-myb-transformed cells and allowing their final myeloid differentiation steps to occur. We found that the retinoic acid receptor α inhibits v-Myb transformation by suppressing the expression of v-Myb target genes typified by themim-1 gene. Conversely, v-Myb protein interferes with RARα transactivation function as well as with retinoic acid-induced apoptosis of HL-60 cells. These results demonstrate that retinoic acid receptor and v-Myb proteins act in antagonistic ways and reciprocally modify each otherʹs functions.