tretinoin and zinc-chloride

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-myb acts 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 differentiation 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 protein interferes with RAR alpha 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 other's functions.

Topics: Acetyltransferases; Animals; Apoptosis; Cell Differentiation; Cell Transformation, Neoplastic; Chlorides; Coturnix; Fibroblasts; Gene Expression Regulation; Gene Expression Regulation, Leukemic; Hematopoiesis; Hematopoietic Stem Cells; HL-60 Cells; Humans; Oncogene Proteins v-myb; Protein Biosynthesis; Proteins; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Retroviridae Proteins, Oncogenic; Transcription, Genetic; Tretinoin; Zinc Compounds