Regulation of RUNX1 transcriptional function by GATA-1
Regulation of RUNX1 transcriptional function by GATA-1
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DOI：
10.1615/critreveukargeneexpr.v17.i4.20
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发表时间：
2007-01-01
影响因子：
1.6
通讯作者：
Goldfarb, Adam N.
中科院分区：
文献类型：
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作者：
Elagib, Kamaleldin E.;Goldfarb, Adam N.
Runt 相关转录因子 1 (RUNX1) 和 GATA-1 都是已知在造血过程中发挥重要作用的转录因子。每种基因的改变都与血小板发育异常以及白血病易感性有关。此外，体外和动物研究表明这两个因素都参与巨核细胞生成。我们和其他人之前已经表明，RUNX1和GATA-1在巨核细胞启动子（例如α IIb整联蛋白和糖蛋白Ib α）的激活中物理相互作用和合作。此外，RUNX1与GATA-1的转录合作在果蝇中是保守的，其中RUNX1和GATA-1同源物在晶体细胞发育中合作。在本文中，我们将回顾RUNX1之间转录串扰的分子和功能意义。特别是，我们将详细阐述最近的数据，这些数据表明 GATA-1 靶向 RUNX1 进行修饰，特别是通过细胞周期蛋白依赖性激酶进行磷酸化。此外，GATA-1 靶向 RUNX1 进行磷酸化可能会将 RUNX1 从阻遏蛋白转化为激活蛋白，这是转录合作的潜在机制，可能是巨核细胞分化的重要步骤。
Runt-related transcription factor 1 (RUNX1) and GATA-1 are both transcription factors known to play essential roles in hematopoiesis. Genetic alterations of each are associated with abnormal platelet development, as well as predisposition to leukemia. In addition, in vitro and animal studies indicate that both factors are involved in megakaryopoiesis. We and others have previously shown that RUNX1 and GATA-1 physically interact and cooperate in the activation of megakaryocytic promoters such as (alpha IIb integrin and glycoprotein Ib alpha. Moreover, transcriptional cooperation of RUNX1 with GATA-1 is conserved back to Drosophila in which RUNX1 and GATA-1 homologs cooperate in crystal cell development. In this article, we will review the molecular and functional significance of the transcriptional cross talk between RUNX1 and GATA-1. In particular, we will elaborate on recent data which suggest that GATA-1 targets RUNX1 for modification, in particular phosphorylation by cyclin-dependent kinases. Furthermore, targeting of RUNX1 by GATA-1 for phosphorylation may convert RUNX1 from a repressor to an activator. This is a potential mechanism of transcriptional cooperation and may be an essential step in megakaryocytic differentiation.