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The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog

文献类型：期刊论文

作者Jin, Jiali5,6; Liu, Jian1,7; Chen, Cong5,6; Liu, Zhenping8; Jiang, Cong5,6; Chu, Hongshang5,6; Pan, Weijuan5,6; Wang, Xinbo5,6; Zhang, Lingqiang2; Li, Bin3
刊名NATURE COMMUNICATIONS
出版日期2016-11-25
卷号7
ISSN号2041-1723
DOI10.1038/ncomms13594
文献子类Article
英文摘要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.
WOS关键词SELF-RENEWAL ; GROUND-STATE ; PLURIPOTENCY ; TRANSCRIPTION ; PHOSPHORYLATION ; PROTEIN ; EXPRESSION ; DIFFERENTIATION ; MAINTENANCE ; INHIBITOR
资助项目Ministry of Science and Technology of China (973 program)[2012CB910404] ; Ministry of Science and Technology of China (973 program)[2015CB964503] ; Chinese Academy of Sciences[XDA01040301] ; National Natural Science Foundation of China[91519322] ; National Natural Science Foundation of China[91440104] ; National Natural Science Foundation of China[31222037] ; National Natural Science Foundation of China[31171338] ; National Natural Science Foundation of China[81502559] ; National Natural Science Foundation of China[81425024] ; National Natural Science Foundation of China[31371511] ; Doctoral Fund of Ministry of Education of China[20130076110022]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000388641000001
源URL[http://119.78.100.183/handle/2S10ELR8/275797]  
专题国家新药筛选中心
通讯作者Xie, Xin; Wang, Ping
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China;
2.Beijing Inst Radiat Med, Collaborat Innovat Ctr Canc Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing 100850, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol,Unit Mol Immunol, Shanghai 200031, Peoples R China;
4.Tongji Univ, Shanghai Peoples Hosp 10, Dept Clin Med, Shanghai 200072, Peoples R China
5.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China;
6.East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China;
7.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Key Lab Receptor Res, Shanghai 201203, Peoples R China;
8.Tongji Univ, Sch Life Sci & Technol, Shanghai Peoples Hosp 10, Dept Cent Lab, Shanghai 200072, Peoples R China;
推荐引用方式
GB/T 7714		 Jin, Jiali,Liu, Jian,Chen, Cong,et al. The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog[J]. NATURE COMMUNICATIONS,2016,7.
APA Jin, Jiali.,Liu, Jian.,Chen, Cong.,Liu, Zhenping.,Jiang, Cong.,...&Wang, Ping.(2016).The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog.NATURE COMMUNICATIONS,7.
MLA Jin, Jiali,et al."The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog".NATURE COMMUNICATIONS 7(2016).

入库方式： OAI收割

来源：上海药物研究所

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