The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation
The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation
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DOI：
10.1111/j.1365-2443.2005.00906.x
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发表时间：
2005-12-01
期刊：
影响因子：
2.1
通讯作者：
Matsui, T
中科院分区：
文献类型：
--
作者：
Urahama, N;Ito, M;Matsui, T
甲状腺激素受体相关多肽转录共激活复合体(TRAP/Mediator Complex)的TRAP220亚基是酵母介体复合体的哺乳动物亚基，被认为通过与核受体的物理作用作用于一系列重大和特定的生物事件。维生素D受体(VDR)和维甲酸受体(RAR)与维甲酸X受体(RXR)是核受体，分别对单核细胞和粒系细胞起重要作用。在这项研究中，我们介绍了TRAP220在核受体介导的单核细胞和粒细胞生成中的作用。小鼠TRap220(-/-)卵黄囊造血祖细胞对1，25-二羟基维生素D-3刺激的单核/巨噬细胞分化具有抵抗力。此外，流式细胞仪分析显示，TRAP220表达下调的人早幼粒白血病细胞株HL-60在1，25-二羟基维生素D-3和全反式维甲酸的刺激下不能有效地分化为单核细胞和粒细胞。在基因敲除细胞中，VDR或RAR的直接靶基因以及分化标志基因的表达水平较低。这些结果表明，TRAP220在哺乳动物造血中VDR和RAR介导的粒单核细胞分化过程中起着关键作用。
The TRAP220 subunit of the thyroid hormone receptor-associated polypeptide transcription coactivator complex (TRAP/Mediator complex), mammalian counterpart of the yeast Mediator complex, is proposed to act on a variety of major and specific biological events through physical interactions with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. In this study, we present the functional role of TRAP220 in nuclear receptor-mediated monopoiesis and granulopoiesis. The mouse Trap220(-/-) yolk sac hematopoietic progenitor cells were resistant to 1,25-dihydroxyvitamin D-3-stimulated differentiation into monocytes/macrophages. Furthermore, flow cytometric analyses showed that HL-60 cells, human promyelocytic leukemia cell line, wherein TRAP220 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25-dihydroxyvitamin D-3 and all-trans retinoic acid, correspondingly. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells. These results indicated a crucial role of TRAP220 in the optimal VDR- and RAR-mediated myelomonocytic differentiation processes in mammalian hematopoiesis.