The importance of PU.1 concentration in hematopoietic lineage commitment and maturation
The importance of PU.1 concentration in hematopoietic lineage commitment and maturation
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DOI：
10.1016/s1079-9796(03)00152-9
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发表时间：
2003-09-01
影响因子：
2.3
通讯作者：
Simon, MC
中科院分区：
文献类型：
--
作者：
Dahl, R;Simon, MC
PU1是一种ETS家族转录因子，是髓系细胞和淋巴系细胞发育所必需的。由于PU.1对于几种不同的谱系都是必需的，目前还不清楚PU.1在决定造血祖细胞是否分化为巨噬细胞、粒细胞或B细胞方面具有什么作用。最近的研究表明，不同细胞浓度的PU1可能决定着不同的细胞命运，巨噬细胞发育所需的PU.1浓度最高，粒细胞和B细胞命运所需的浓度较低。由于PU.1反式激活活性被粒细胞因子C/EBPalpha和B细胞因子BSAP抑制，巨噬细胞的发育可能需要高浓度的PU.1，以克服替代谱系特异性因子的负面影响。最后，一旦髓系细胞致力于巨噬细胞和粒细胞系，PU.1上调与髓系细胞的成熟有关。在某些急性髓系白血病(AML)中，PU1活性受到抑制，因此，抑制PU1诱导的成熟可能是白血病发生的关键步骤。(C)2003 Elsevier Inc.保留所有权利。
PU.1 is an Ets family transcription factor that is required for the development of myeloid and lymphoid cells. Since PU.1 is required for several different lineages it has been unclear what role PU.1 has in deciding whether a hematopoietic progenitor cell differentiates into a macrophage, granulocyte, or B cell. Recent studies have demonstrated that different cellular concentrations of PU.1 may direct distinct cell fates, with the highest concentrations of PU.1 required for macrophage development and lower concentrations for granulocytic and B-cell fate adoption. Since PU.1 transactivation activity is inhibited by the granulocytic factor, C/EBPalpha and the B-cell factor BSAP, high concentrations of PU.1 may be required for macrophage development in order to overcome the negative effects of alternative lineage specific factors. Lastly, PU.1 Upregulation is implicated in the maturation of myeloid cells once they have committed to the macrophage and granulocytic lineages. PU.1 activity is inhibited in some cases of acute myelogenous leukemia (AML), therefore, inhibition of PU.1 induced maturation may he a critical step in leukemogenesis. (C) 2003 Elsevier Inc. All rights reserved.