Importin alpha subtypes determine differential transcription factor localization in embryonic stem cells maintenance
Importin alpha subtypes determine differential transcription factor localization in embryonic stem cells maintenance
复制标题
输入α亚型决定胚胎干细胞维持中转录因子的差异定位
DOI：
10.1016/j.devcel.2013.06.022
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Yoneda Y.
中科院分区：
文献类型：
--
作者：
Yasuhara N;Yamagishi R;Arai Y;Mehmood R;Kimoto C;Fujita T;Touma K;Kaneko A;Kamikawa Y;Moriyama T;Yanagida T;Kaneko H;Yoneda Y.
我们最近证实，在小鼠胚胎干细胞(ESCs)的神经分化过程中，Importinα亚型的表达从α2转换为α1，并且这种转换对细胞分化有重要影响。在这项研究中，我们报道了一种决定细胞命运的机制，其中Importinα2负向调节某些转录因子的核输入，以维持胚胎干细胞的特性。Oct6和Brn2的核进口是通过与Importinα2中的核定位信号结合位点结合的货物形成运输不能的复合体来抑制的。除非这种显性-负性效应在胚胎干细胞分化过程中被下调，否则会诱导不适当的细胞死亡。我们认为，虽然某些转录因子是胚胎干细胞分化所必需的，但这些因子通过导入α2保留在细胞质中，从而阻止转录因子在细胞核中的活性，直到细胞经历分化。
We recently demonstrated that the expression of the importin α subtype is switched from α2 to α1 during neural differentiation in mouse embryonic stem cells (ESCs) and that this switching has a major impact on cell differentiation. In this study, we report a cell-fate determination mechanism in which importin α2 negatively regulates the nuclear import of certain transcription factors to maintain ESC properties. The nuclear import of Oct6 and Brn2 was inhibited via the formation of a transport-incompetent complex of the cargo bound to a nuclear localization signal binding site in importin α2. Unless this dominant-negative effect was downregulated upon ESC differentiation, inappropriate cell death was induced. We propose that although certain transcription factors are necessary for differentiation in ESCs, these factors are retained in the cytoplasm by importin α2, thereby preventing transcription factor activity in the nucleus until the cells undergo differentiation.