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-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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Acetyltransferases*
-
Animals
-
Apoptosis / drug effects
-
Cell Differentiation / drug effects
-
Cell Differentiation / physiology
-
Cell Transformation, Neoplastic
-
Chlorides / pharmacology
-
Coturnix
-
Fibroblasts / drug effects
-
Gene Expression Regulation / drug effects
-
Gene Expression Regulation / physiology
-
Gene Expression Regulation, Leukemic / drug effects
-
HL-60 Cells / drug effects
-
Hematopoiesis / drug effects
-
Hematopoiesis / physiology*
-
Hematopoietic Stem Cells / cytology
-
Hematopoietic Stem Cells / drug effects
-
Hematopoietic Stem Cells / metabolism
-
Humans
-
Oncogene Proteins v-myb
-
Protein Biosynthesis
-
Proteins / genetics
-
Receptors, Retinoic Acid / antagonists & inhibitors
-
Receptors, Retinoic Acid / physiology*
-
Retinoic Acid Receptor alpha
-
Retroviridae Proteins, Oncogenic / antagonists & inhibitors
-
Retroviridae Proteins, Oncogenic / physiology*
-
Transcription, Genetic / drug effects
-
Transcription, Genetic / physiology*
-
Tretinoin / pharmacology
-
Zinc Compounds / pharmacology
Substances
-
Chlorides
-
Oncogene Proteins v-myb
-
Proteins
-
RARA protein, human
-
Receptors, Retinoic Acid
-
Retinoic Acid Receptor alpha
-
Retroviridae Proteins, Oncogenic
-
Zinc Compounds
-
Tretinoin
-
zinc chloride
-
Acetyltransferases
-
mim-1 protein, Gallus gallus