FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1.
FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1.
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DOI：
10.1083/jcb.200307056
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发表时间：
2004-01-19
期刊：
影响因子：
--
通讯作者：
van Dijk TB
中科院分区：
文献类型：
--
作者：
Bakker WJ;Blázquez-Domingo M;Kolbus A;Besooyen J;Steinlein P;Beug H;Coffer PJ;Löwenberg B;von Lindern M;van Dijk TB
红细胞生成需要严格控制红系祖细胞的扩增、成熟和存活。由于激活磷脂酰肌醇-3-激酶（PI 3 K）是红细胞生成素/干细胞因子诱导的红系祖细胞扩增所必需的，我们研究了PI 3 K控制的叉头盒，O类（FoxO）叉头转录因子亚家族的作用。FoxO 3a的表达和核积累在红系分化过程中增加，而过早诱导FoxO 3a活性加速红系祖细胞向红细胞的分化。我们鉴定了B细胞易位基因1（BTG 1）/抗增殖蛋白2作为红系祖细胞中FoxO 3a靶基因。启动子研究表明BTG 1是FoxO 3a的直接靶点。BTG 1在原代小鼠骨髓细胞中的表达阻断了红系集落的生长，这需要结合蛋白质精氨酸甲基转移酶1的BTG 1结构域。在红系分化过程中，精氨酸甲基化增加与BTG 1表达一致。一致地，甲基转移酶活性的抑制阻断红系成熟而不影响祖细胞的扩增。我们提出FoxO 3a控制BTG 1的表达和随后的蛋白质精氨酸甲基转移酶活性的调节作为控制红细胞扩增和分化的一种新机制。
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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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.2
作者：
Cimato, TR;Tang, J;Aletta, JM
通讯作者：
Aletta, JM
影响因子：
20.3
作者：
Kashii, Y;Uchida, M;Komatsu, N
通讯作者：
Komatsu, N
影响因子：
20.3
作者：
Bao, HF;Jacobs-Helber, SM;Sawyer, ST
通讯作者：
Sawyer, ST
DOI：
10.1073/pnas.94.7.3016
发表时间：
1997-04-01
影响因子：
11.1
作者：
Klingmuller, U;Wu, H;Lodish, HF
通讯作者：
Lodish, HF