The notch intracellular domain can function as a coactivator for LEF-1
The notch intracellular domain can function as a coactivator for LEF-1
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DOI：
10.1128/mcb.21.22.7537-7544.2001
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发表时间：
2001-11-01
影响因子：
5.3
通讯作者：
Kadesch, T
中科院分区：
文献类型：
--
作者：
Ross, DA;Kadesch, T
Notch 信号传导始于两个配体介导的蛋白水解事件，这些事件从质膜释放 Notch 胞内结构域 NICD。然后 NICD 易位到细胞核中并与 DNA 结合蛋白 CSL 相互作用以激活转录。我们发现 NICD 表达还增强转录因子 LEF-1 的活性。 NICD 对 LEF-1 活性的刺激是环境依赖性的，并且发生在与 β-连环蛋白激活的启动子不同的启动子子集上。重要的是，NICD 的作用似乎不是通过 Wnt 信号通路的经典成分或 Notch 通路的下游成分介导的。体外测定显示 NICD 的 C 端反式激活结构域和 LEF-1 的高迁移率基团结构域之间的弱关联，表明这两种蛋白在体内相互作用。因此，我们的数据描述了 Notch 信号传导的新核靶点和 LEF-1 的新共激活因子。
Notch signaling commences with two ligand-mediated proteolysis events that release the Notch intracellular domain, NICD, from the plasma membrane. NICD then translocates into the nucleus and interacts with the DNA binding protein CSL to activate transcription. We found that NICD expression also potentiates activity of the transcription factor LEF-1. NICD stimulation of LEF-1 activity was context dependent and occurred on a subset of promoters distinct from those activated by beta -catenin. Importantly, the effect of NICD does not appear to be mediated through canonical components of the Wnt signaling pathway or downstream components of the Notch pathway. In vitro assays show a weak association between the C-terminal transactivation domain of NICD and the high-mobility group domain of LEF-1, suggesting that the two proteins interact in vivo. Our data therefore describe a new nuclear target of Notch signaling and a new coactivator for LEF-1.