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FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1

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 Fo...

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Autores principales: Bakker, Walbert J., Blázquez-Domingo, Montserrat, Kolbus, Andrea, Besooyen, Janey, Steinlein, Peter, Beug, Hartmut, Coffer, Paul J., Löwenberg, Bob, von Lindern, Marieke, van Dijk, Thamar B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172323/
https://www.ncbi.nlm.nih.gov/pubmed/14734530
http://dx.doi.org/10.1083/jcb.200307056
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author Bakker, Walbert J.
Blázquez-Domingo, Montserrat
Kolbus, Andrea
Besooyen, Janey
Steinlein, Peter
Beug, Hartmut
Coffer, Paul J.
Löwenberg, Bob
von Lindern, Marieke
van Dijk, Thamar B.
author_facet Bakker, Walbert J.
Blázquez-Domingo, Montserrat
Kolbus, Andrea
Besooyen, Janey
Steinlein, Peter
Beug, Hartmut
Coffer, Paul J.
Löwenberg, Bob
von Lindern, Marieke
van Dijk, Thamar B.
author_sort Bakker, Walbert J.
collection PubMed
description 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.
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spelling pubmed-21723232008-03-05 FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1 Bakker, Walbert J. Blázquez-Domingo, Montserrat Kolbus, Andrea Besooyen, Janey Steinlein, Peter Beug, Hartmut Coffer, Paul J. Löwenberg, Bob von Lindern, Marieke van Dijk, Thamar B. J Cell Biol Article 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. The Rockefeller University Press 2004-01-19 /pmc/articles/PMC2172323/ /pubmed/14734530 http://dx.doi.org/10.1083/jcb.200307056 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Bakker, Walbert J.
Blázquez-Domingo, Montserrat
Kolbus, Andrea
Besooyen, Janey
Steinlein, Peter
Beug, Hartmut
Coffer, Paul J.
Löwenberg, Bob
von Lindern, Marieke
van Dijk, Thamar B.
FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
title FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
title_full FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
title_fullStr FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
title_full_unstemmed FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
title_short FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
title_sort foxo3a regulates erythroid differentiation and induces btg1, an activator of protein arginine methyl transferase 1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172323/
https://www.ncbi.nlm.nih.gov/pubmed/14734530
http://dx.doi.org/10.1083/jcb.200307056
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