Ski negatively regulates erythroid differentiation through its interaction with GATA1.
Ski negatively regulates erythroid differentiation through its interaction with GATA1.
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Ski 通过与 GATA1 的相互作用负向调节红细胞分化。
DOI：
10.1128/mcb.24.23.10118-10125.2004
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发表时间：
2004
影响因子：
5.3
通讯作者：
Hayman,MichaelJ
中科院分区：
文献类型：
--
作者：
Ueki,Nobuhide;Zhang,Leiqing;Hayman,MichaelJ
Ski癌蛋白显著影响细胞生长、分化和/或存活。最近，Ski被证明在不同的信号通路中起作用，包括涉及核受体、转化生长因子β和肿瘤抑制因子的信号通路。Ski的这些不同角色可能取决于Ski将具有不同功能的多个合作伙伴绑定在一起的能力。特别是，Ski改变了红系祖细胞的生长和分化程序，导致恶性白血病。然而，这一重要影响的机制仍然难以捉摸。在这里，我们表明，滑雪与GATA 1，在红细胞生成中必不可少的转录因子相互作用。使用GATA 1结合缺陷的Ski突变体，我们表明这种Ski-GATA 1相互作用对于Ski抑制GATA 1介导的转录和阻断红细胞分化的能力至关重要。此外，GATA 1介导的转录的抑制涉及Ski阻断GATA 1的DNA结合的能力。这一发现是在显着的对比，在以前的报告中的机制，由滑雪，其中描述了一个模型，涉及招聘corepressors到DNA结合的转录复合物的镇压。我们认为Ski通过干扰GATA 1功能来参与红系细胞的转化过程，从而导致红白血病。
The Ski oncoprotein dramatically affects cell growth, differentiation, and/or survival. Recently, Ski was shown to act in distinct signaling pathways including those involving nuclear receptors, transforming growth factor β, and tumor suppressors. These divergent roles of Ski are probably dependent on Ski's capacity to bind multiple partners with disparate functions. In particular, Ski alters the growth and differentiation program of erythroid progenitor cells, leading to malignant leukemia. However, the mechanism underlying this important effect has remained elusive. Here we show that Ski interacts with GATA1, a transcription factor essential in erythropoiesis. Using a Ski mutant deficient in GATA1 binding, we show that this Ski-GATA1 interaction is critical for Ski's ability to repress GATA1-mediated transcription and block erythroid differentiation. Furthermore, the repression of GATA1-mediated transcription involves Ski's ability to block DNA binding of GATA1. This finding is in marked contrast to those in previous reports on the mechanism of repression by Ski, which have described a model involving the recruitment of corepressors into DNA-bound transcription complexes. We propose that Ski cooperates in the process of transformation in erythroid cells by interfering with GATA1 function, thereby contributing to erythroleukemia.