ONCOPROTEIN V-MYB AND RETINOIC ACID RECEPTOR-ALPHA ARE MUTUAL ANTAGONISTS

The process of hematopoiesis is critically dependent on correct intera ctions 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-myb act s as a transforming oncogene preventing differentiation of monoblasts to macrophages, RAR alpha functions as an anti-oncogene arresting the growth of v-myb-transformed cells and allowing their final myeloid dif ferentiation steps to occur. We found that the retinoic acid receptor alpha inhibits v-Myb transformation by suppressing the expression of v -Myb target genes typified by the mim-1 gene. Conversely, v-Myb protei n interferes with RAR alpha transactivation function as well as with r etinoic acid-induced apoptosis of HL-60 cells. These results demonstra te that retinoic acid receptor and v-Myb proteins act in antagonistic ways and reciprocally modify each other's functions. (C) 1998 Academic Press.