Destabilizing LSD1 by Jade-2 Promotes Neurogenesis: An Antibraking System in Neural Development

被引：108

作者：

Han, Xiao ^{[1
]}

Gui, Bin ^{[1
]}

Xiong, Cong ^{[3
]}

Zhao, Linnan ^{[4
]}

Liang, Jing ^{[1
]}

Sun, Luyang ^{[1
]}

Yang, Xiaohan ^{[1
]}

Yu, Wenhua ^{[1
]}

Si, Wenzhe ^{[1
]}

Yan, Ruorong ^{[1
]}

Yi, Xia ^{[1
]}

Zhang, Di ^{[1
]}

Li, Wanjin ^{[1
]}

Li, Lifang ^{[1
]}

Yang, Jianguo ^{[1
]}

Wang, Yan ^{[2
]}

Sun, Yi Eve ^{[5
,6
,7
]}

Zhang, Dai ^{[4
]}

Meng, Anming ^{[3
]}

Shang, Yongfeng ^{[1
,2
]}

机构：

[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

来源：

MOLECULAR CELL | 2014年 / 55卷 / 03期

基金：

中国国家自然科学基金;

关键词：

EMBRYONIC STEM-CELLS; UBIQUITIN LIGASE HUWE1; ZINC-FINGER PROTEIN; DEMETHYLASE LSD1; TUMOR-SUPPRESSOR; RETINOIC ACID; DIFFERENTIATION; PROLIFERATION; GENE; EXPRESSION;

D O I：

10.1016/j.molcel.2014.06.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

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.

引用

页码：482 / 494

页数：13

共 44 条

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