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Destabilizing LSD1 by Jade-2 Promotes Neurogenesis: An Antibraking System in Neural Development
Han, Xiao1; Gui, Bin1; Xiong, Cong3; Zhao, Linnan4; Liang, Jing1; Sun, Luyang1; Yang, Xiaohan1; Yu, Wenhua1; Si, Wenzhe1; Yan, Ruorong1; Yi, Xia1; Zhang, Di1; Li, Wanjin1; Li, Lifang1; Yang, Jianguo1; Wang, Yan2; Sun, Yi Eve5,6,7; Zhang, Dai4; Meng, Anming3; Shang, Yongfeng1,2
刊名MOLECULAR CELL
2014-08-07
DOI10.1016/j.molcel.2014.06.006
55期:3页:482-494
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]EMBRYONIC STEM-CELLS ; UBIQUITIN LIGASE HUWE1 ; ZINC-FINGER PROTEIN ; DEMETHYLASE LSD1 ; TUMOR-SUPPRESSOR ; RETINOIC ACID ; DIFFERENTIATION ; PROLIFERATION ; GENE ; EXPRESSION
英文摘要

Histone H3K4 demethylase LSD1 plays an important role in stem cell biology, especially in the maintenance of the silencing of differentiation genes. However, how the function of LSD1 is regulated and the differentiation genes are derepressed are not understood. Here, we report that elimination of LSD1 promotes embryonic stem cell (ESC) differentiation toward neural lineage. We showed that the destabilization of LSD1 occurs posttranscriptionally via the ubiquitin-proteasome pathway by an E3 ubiquitin ligase, Jade-2. We demonstrated that Jade-2 is a major LSD1 negative regulator during neurogenesis in vitro and in vivo in both mouse developing cerebral cortices and zebra fish embryos. Apparently, Jade2-mediated degradation of LSD1 acts as an antibraking system and serves as a quick adaptive mechanism for re-establishing epigenetic landscape without more laborious transcriptional regulations. As a potential anticancer strategy, Jade-2-mediated LSD1 degradation could potentially be used in neuroblastoma cells to induce differentiation toward postmitotic neurons.

语种英语
WOS记录号WOS:000340646600013
项目编号81130048 ; 30921062 ; 2011CB504204 ; 2014CB542004
资助机构National Natural Science Foundation of China ; Ministry of Science and Technology of China (973 Program)
引用统计
被引频次:27[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65311
专题北京大学精神卫生研究所
北京大学医学部管理机构_医学部
北京大学基础医学院
北京大学第一临床医学院_妇产科
北京大学第三临床医学院_检验科
北京大学第三临床医学院_眼科
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100191, Peoples R China
2.Tianjin Med Univ, Dept Biochem & Mol Biol, Tianjin Key Lab Med Epigenet, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Tianjin 300070, Peoples R China
3.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Biomembrane & Membrane Engn, Beijing 100084, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Minist Hlth, Key Lab Mental Hlth, Beijing 100191, Peoples R China
5.Tongji Univ, Sch Med, Stem Cell Res Ctr, Translat Ctr Stem Cell Res,Tongji Hosp, Shanghai 200065, Peoples R China
6.Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA
7.Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
推荐引用方式
GB/T 7714
Han, Xiao,Gui, Bin,Xiong, Cong,et al. Destabilizing LSD1 by Jade-2 Promotes Neurogenesis: An Antibraking System in Neural Development[J]. MOLECULAR CELL,2014,55(3):482-494.
APA Han, Xiao.,Gui, Bin.,Xiong, Cong.,Zhao, Linnan.,Liang, Jing.,...&Shang, Yongfeng.(2014).Destabilizing LSD1 by Jade-2 Promotes Neurogenesis: An Antibraking System in Neural Development.MOLECULAR CELL,55(3),482-494.
MLA Han, Xiao,et al."Destabilizing LSD1 by Jade-2 Promotes Neurogenesis: An Antibraking System in Neural Development".MOLECULAR CELL 55.3(2014):482-494.
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