The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog.
The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog.
复制标题
去泛素酶 USP21 通过 Nanog 的稳定性维持小鼠胚胎干细胞的干性
DOI：
10.1038/ncomms13594
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发表时间：
2016-11-25
影响因子：
16.6
通讯作者：
Wang, Ping
中科院分区：
文献类型：
--
作者：
Jin, Jiali;Liu, Jian;Chen, Cong;Liu, Zhenping;Jiang, Cong;Chu, Hongshang;Pan, Weijuan;Wang, Xinbo;Zhang, Lingqiang;Li, Bin;Jiang, Cizhong;Ge, Xin;Xie, Xin;Wang, Ping
Nanog是胚胎干细胞(ESCs)的主要多能性因子。Nanog的稳定表达对于维持胚胎干细胞的干性是必不可少的。然而，Nanog是一种短暂的蛋白质，并被泛素依赖的蛋白酶体系统迅速降解。在这里，我们报道了去泛素酶USP21与Nanog相互作用，去泛素化和稳定Nanog，从而维持小鼠ESCs中Nanog的蛋白水平。USP21的缺失会导致Nanog降解，mESCs分化，并降低体细胞重新编程的效率。USP21是LIF/STAT3途径的转录靶点，在分化过程中下调。此外，分化信号促进ERK介导的USP21与Nanog的磷酸化和解离，从而导致Nanog的降解。此外，USP21被Nanog招募到基因启动子，使K119位的组蛋白H2A去泛素化，从而促进Nanog介导的基因表达。总之，我们的发现提供了一种调控机制，外部信号通过去泛素化Nanog来调节mESC的命运。
Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable expression of Nanog is essential to maintain the stemness of ESCs. However, Nanog is a short-lived protein and quickly degraded by the ubiquitin-dependent proteasome system. Here we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs). Loss of USP21 results in Nanog degradation, mESCs differentiation and reduces somatic cell reprogramming efficiency. USP21 is a transcriptional target of the LIF/STAT3 pathway and is downregulated upon differentiation. Moreover, differentiation cues promote ERK-mediated phosphorylation and dissociation of USP21 from Nanog, thus leading to Nanog degradation. In addition, USP21 is recruited to gene promoters by Nanog to deubiquitinate histone H2A at K119 and thus facilitates Nanog-mediated gene expression. Together, our findings provide a regulatory mechanism by which extrinsic signals regulate mESC fate via deubiquitinating Nanog.
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DOI：
10.1098/rsif.2012.0525
发表时间：
2013-01-06
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Luo Y;Lim CL;Nichols J;Martinez-Arias A;Wernisch L
通讯作者：
Wernisch L
影响因子：
23.9
作者：
Buckley, Shannon M.;Aranda-Orgilles, Beatriz;Strikoudis, Alexandros;Apostolou, Effie;Loizou, Evangelia;Moran-Crusio, Kelly;Farnsworth, Charles L.;Koller, Antonius A.;Dasgupta, Ramanuj;Silva, Jeffrey C.;Stadtfeld, Matthias;Hochedlinger, Konrad;Chen, Emily I.;Aifantis, Iannis
通讯作者：
Aifantis, Iannis
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
影响因子：
4.8
作者：
Ho, Baotran;Olson, Gretchen;Golubovskaya, Vita M.
通讯作者：
Golubovskaya, Vita M.