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Mutations of nuclear localization signals in mNANOG generate dominant negative mutants
  • ISSN号:1001-6538
  • 期刊名称:科学通报(英文版)
  • 时间:0
  • 页码:1361-1368
  • 语言:中文
  • 分类:Q26[生物学—细胞生物学] S511[农业科学—作物学]
  • 作者机构:[1]Laboratory of Stem Cell Biology, Department of Biological Sciences & Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institutes of Biomedicine, School of Medicine, Tsinghua University, Beijing 100084, China, [2]Stem Cell and Cancer Biology Group, Key Laboratory of Regenerative Biology, South China Institute for Stern Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China
  • 相关基金:Supported by National Natural Science Foundation of China (Grant Nos. 30725012, 30630039 and 90813033), Knowledge Innovation Project of Chinese Academy of Sciences (Grant No. KSCX2-YW-R-48), Guangzhou Science and Technology Com- mission Foundation (Grant No. 2008AI-E4011), and National Key Basic Research and Development Program of China (Grant Nos. 2006CB701504, 2006CB943600, 2007CB948002 and 2007CB947804)
  • 相关项目:干细胞全能性与分化的分子机制研究
中文摘要:

老鼠 NANOG 在维持胚胎的干细胞的自强和 pluripotency 起一个关键作用。然而, mNANOG 怎么工作的精确机制仍然少些被知道。这里,我们报导鼠标 NANOG 有在保存 homeobox 域为原子本地化和 transcriptional 活动负责的二个原子本地化信号(NLS, RKQKMR 和 RMKCKR ) 。老鼠 NANOG 的 NLS 异种产生在整个房间是局部性的并且失去 transactivation 功能的 3 异种。我们进一步证明所有三 NLS 异种可以自己与野类型的老鼠 NANOG 相似 NANOG dimerization 交往并且禁止野类型的老鼠 NANOG 活动,充当主导的否定异种。鼠标 NANOG 的 NLS 异种可以也在 pluripotent 房间禁止 oct4 倡导者的活动,显示 NLS 异种能影响在 vivo 的内长的鼠标 NANOG 函数。这些数据建议老鼠 NANOG 的 NLS 异种可以被用作一个工具在 pluripotent 房间调整 NANOG 活动。

英文摘要:

Mouse NANOG plays a critical role in maintaining self-renewal and pluripotency of embryonic stem cells. Yet, the precise mechanism of how mNANOG functions is still less known. Here, we report that mouse NANOG has two nuclear localization signals (NLS, RKQKMR and RMKCKR) which are respon- sible for the nuclear localization and transcriptional activity in the conserved homeobox domain. NLS mutants of mouse NANOG generate 3 mutants that are localized throughout the cells and lose the transactivation function. We further prove that all three NLS mutants may interact with the wild-type mouse NANOG like NANOG dimerization itself and inhibit the wild-type mouse NANOG activity, acting as dominant negative mutants. The NLS mutants of mouse NANOG may also inhibit activity of oct4 promoter in pluripotent cells, indicating that the NLS mutants can affect the endogenous mouse NANOG function in vivo. These data suggest that the NLS mutants of mouse NANOG may be used as a tool to regulate NANOG activity in pluripotent cells.

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