β-catenin up-regulates Nanog expression through interaction with Oct-3/4 in embryonic stem cells

β-catenin up-regulates Nanog expression through interaction with Oct-3/4 in embryonic stem cells
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DOI:
10.1016/j.bbrc.2006.12.072
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发表时间:
2007-02-16
影响因子:
3.1
通讯作者:
Koide, Hiroshi
Koide, Hiroshi
中科院分区:
生物学4区
文献类型:
--
作者:
Takao, Yukinari;Yokota, Takashi;Koide, Hiroshi

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众所周知,小鼠胚胎干细胞(ES)可以通过白血病抑制因子(LIF)的存在来维持。最近的研究表明,Wnt也表现出类似于LIF的活性。然而,这些因子维持ES细胞的分子机制尚未完全了解。在这项研究中,我们发现LIF增强核β-连环蛋白的水平,Wnt信号通路的一个组成部分。β-连环蛋白的激活突变体的表达导致ES细胞的长期增殖,即使在没有LIF的情况下。此外,发现β-连环蛋白以Oct-3/4依赖性方式上调Nanog,并且β-连环蛋白与Oct-3/4物理缔合。这些结果表明,通过与Oct-3/4相互作用上调Nanog涉及P-连环蛋白在LIF和Wnt介导的ES细胞自我更新的维持。(c)2006年爱思唯尔公司All rights reserved.
It is well known that mouse embryonic stem (ES) cells can be maintained by the presence of leukemia inhibitory factor (LIF). Recent studies have revealed that Wnt also exhibits activity similar to LIF. The molecular mechanism behind the maintenance of ES cells by these factors, however, is not fully understood. In this study, we found that LIF enhances level of nuclear beta-catenin, a component of the Wnt signaling pathway. Expression of an activated mutant of beta-catenin led to the long-term proliferation of ES cells, even in the absence of LIF. Furthermore, it was found that beta-catenin up-regulates Nanog in an Oct-3/4-dependent manner and that P-catenin physically associates with Oct-3/4. These results suggest that up-regulating Nanog through interaction with Oct-3/4 involves P-catenin in the LIF- and Wnt-mediated maintenance of ES cell self-renewal. (c) 2006 Elsevier Inc. All rights reserved.