Oncoprotein v-Myb and retinoic acid receptor alpha are mutual antagonists.
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.
Department of Cellular and Molecular Oncology, Masaryk Institute of Oncology, Brno, Czech Republic.
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K
Zemanová
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Smarda
D000123:Acetyltransferases; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D002712:Chlorides / Q000494:pharmacology; D003370:Coturnix; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020626:Oncogene Proteins v-myb; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D015682:Retroviridae Proteins, Oncogenic / Q000037:antagonists & inhibitors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D020626:Oncogene Proteins v-myb; D011506:Proteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D015682:Retroviridae Proteins, Oncogenic; D017967:Zinc Compounds; D014212:Tretinoin; C016837:zinc chloride; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus