FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
| Autor: | Andrea Kolbus, Marieke von Lindern, Bob Löwenberg, Montserrat Blázquez-Domingo, Janey Besooyen, Walbert Bakker, Paul J. Coffer, Thamar B. van Dijk, Peter Steinlein, Hartmut Beug |
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| Přispěvatelé: | Other departments, Landsteiner Laboratory, Faculteit Medische Wetenschappen/UMCG, Hematology |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Protein-Arginine N-Methyltransferases
Arginine PRMT1 Cellular differentiation MOLECULAR ANALYSIS FORKHEAD TRANSCRIPTION FACTOR Polymerase Chain Reaction Mice Genes Reporter erythropoiesis Forkhead transcription factors protein arginine methylation cDNA microarray hemic and lymphatic diseases Chlorocebus aethiops FACTOR FKHR-L1 Cloning Molecular STEM-CELL FACTOR Luciferases Promoter Regions Genetic Cells Cultured Oligonucleotide Array Sequence Analysis Forkhead Box Protein O3 Cell Differentiation 3T3 Cells Methylation Neoplasm Proteins APOPTOSIS COS Cells Erythropoiesis PHOSPHATIDYLINOSITOL 3-KINASE EXPRESSION KINASE-B Molecular Sequence Data FACTOR AFX Biology Article Cell Line Animals Humans Progenitor cell Transcription factor DNA Primers Base Sequence Activator (genetics) Cell Biology Hematopoietic Stem Cells Molecular biology Enzyme Activation N-METHYLTRANSFERASE BTG1 Transcription Factors |
| Zdroj: | Journal of cell biology, 164(2), 175-184. Rockefeller University Press Journal of Cell Biology, 164(2), 175-184. ROCKEFELLER UNIV PRESS Journal of Cell Biology, 164, 175-184. Rockefeller University Press The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Erythropoiesis requires tight control of expansion, maturation, and survival of erythroid progenitors. Because activation of phosphatidylinositol-3-kinase (PI3K) is required for erythropoietin/stem cell factor–induced expansion of erythroid progenitors, we examined the role of the PI3K-controlled Forkhead box, class O (FoxO) subfamily of Forkhead transcription factors. FoxO3a expression and nuclear accumulation increased during erythroid differentiation, whereas untimely induction of FoxO3a activity accelerated differentiation of erythroid progenitors to erythrocytes. We identified B cell translocation gene 1 (BTG1)/antiproliferative protein 2 as a FoxO3a target gene in erythroid progenitors. Promoter studies indicated BTG1 as a direct target of FoxO3a. Expression of BTG1 in primary mouse bone marrow cells blocked the outgrowth of erythroid colonies, which required a domain of BTG1 that binds protein arginine methyl transferase 1. During erythroid differentiation, increased arginine methylation coincided with BTG1 expression. Concordantly, inhibition of methyl transferase activity blocked erythroid maturation without affecting expansion of progenitor cells. We propose FoxO3a-controlled expression of BTG1 and subsequent regulation of protein arginine methyl transferase activity as a novel mechanism controlling erythroid expansion and differentiation. |
| Databáze: | OpenAIRE |
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