Transcriptional regulation of erythropoiesis: an affair involving multiple partners
Transcriptional regulation of erythropoiesis: an affair involving multiple partners
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DOI：
10.1038/sj.onc.1205326
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发表时间：
2002-05-13
期刊：
影响因子：
8
通讯作者：
Orkin, SH
中科院分区：
文献类型：
--
作者：
Cantor, AB;Orkin, SH
先前的研究已经表明，谱系特异性转录因子在红细胞发育中起着至关重要的作用。近期更多的研究显示，这些因子除了与DNA结合外，还参与关键的蛋白质 - 蛋白质相互作用。锌指转录因子GATA - 1是红系基因表达的核心调节因子，它与多种蛋白质相互作用，包括FOG - 1、EKLF、SP1、CBP/p300和PU.1。这些相互作用影响GATA - 1功能的机制，以及这些看似不同的复合物之间可能存在的任何关系，仍未完全被理解。然而，一些新的发现为其中一些相互作用的功能意义提供了进一步的见解。涉及GATA - 1点突变的研究表明，GATA - 1和FOG - 1之间的直接物理相互作用对于体内正常的人类红系和巨核细胞成熟至关重要。此外，有证据表明，GATA - 1与髓系/淋巴系特异性因子PU.1（一种与小鼠红白血病有关的癌基因）之间的物理相互作用在功能上相互拮抗。这为造血转录因子表达失调导致白血病中谱系成熟停滞提供了一种可能的机制。
Previous work has demonstrated that lineage-specific transcription factors play essential roles in red blood cell development. More recent studies have shown that these factors participate in critical protein-protein interactions in addition to binding DNA. The zinc finger transcription factor GATA-1, a central mediator of erythroid gene expression, interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1. The mechanisms by which these interactions influence GATA-1 function, as well as any possible relationships between these seemingly disparate complexes, remain incompletely understood. However, several new findings have provided further insight into the functional significance of some of these interactions. Studies involving point mutants of GATA-1 have shown that a direct physical interaction between GATA-I and FOG-1 is essential for normal human erythroid and megakaryocyte maturation in vivo. In addition, evidence has emerged that physical interaction between GATA-I and the myeloid/lymphoid specific factor PU.1, an oncogene implicated in murine erythroleukemia, acts to functionally cross-antagonize one another. This provides a possible mechanism by which dysregulated expression of hematopoietic transcription factors leads to lineage maturation arrest in leukemias.