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学科主题: 精神卫生
题名:
Destabilizing LSD1 by Jade-2 Promotes Neurogenesis: An Antibraking System in Neural Development
作者: 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
发表日期: 2014-08-07
DOI: 10.1016/j.molcel.2014.06.006
卷: 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
所属项目编号: 81130048 ; 30921062 ; 2011CB504204 ; 2014CB542004
项目资助者: National Natural Science Foundation of China ; Ministry of Science and Technology of China (973 Program)
WOS记录号: WOS:000340646600013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65311
Appears in Collections:北京大学精神卫生研究所_期刊论文

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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

Recommended Citation:
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.
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