Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells
Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells
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DOI：
10.1242/jcs.023119
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发表时间：
2008-05-15
影响因子：
4
通讯作者：
Yamaguchi, Akira
中科院分区：
文献类型：
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作者：
Sakamoto, Kei;Tamamura, Yoshihiro;Yamaguchi, Akira
Notch信号传导对于组织和细胞分化的多个方面是必需的。在这项研究中，我们确定了锌指蛋白64（Zfp64）作为一种新的Notch 1的共激活因子。Zfp 64与Notch 1的胞内结构域相关，募集到Notch靶基因Hes 1和Hey 1的启动子，并反式激活它们。Zfp64的表达受Runx2的控制，并通过其启动子的直接反式激活而上调。Zfp 64抑制C2C12细胞的肌源性分化并促进其成骨分化。我们的数据证明了Zfp 64的两种功能：（1）它是Runx 2的下游靶标，（2）其同源蛋白作为Notch 1的共激活因子，这表明Zfp 64通过调节Notch信号传导介导间充质细胞分化。
Notch signaling is required for multiple aspects of tissue and cell differentiation. In this study, we identified zinc finger protein 64 (Zfp64) as a novel coactivator of Notch1. Zfp64 is associated with the intracellular domain of Notch1, recruited to the promoters of the Notch target genes Hes1 and Hey1, and transactivates them. Zfp64 expression is under the control of Runx2, and is upregulated by direct transactivation of its promoter. Zfp64 suppresses the myogenic differentiation of C2C12 cells and promotes their osteoblastic differentiation. Our data demonstrate two functions of Zfp64: (1) it is a downstream target of Runx2 and, (2) its cognate protein acts as a coactivator of Notch1, which suggests that Zfp64 mediates mesenchymal cell differentiation by modulating Notch signaling.