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题名: Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction
作者: Wang, Sheng1; Yin, Junlin2; Chen, Duozhi2; Nie, Fen1; Song, Xiaomin1; Fei, Cong1; Miao, Haofei1; Jing, Changbin3, 4; Ma, Wenjing3, 4; Wang, Lei2; Xie, Sichun1; Li, Chen5; Zeng, Rong5; Pan, Weijun3, 4; null(郝小江)2; Li, Lin1
刊名: NATURE CHEMICAL BIOLOGY
关键词: GLYCOGEN-SYNTHASE KINASE-3 ; BETA-CATENIN ; NEGATIVE REGULATOR ; DIX DOMAIN ; STEM-CELLS ; IN-VIVO ; AXIN ; ACTIVATION ; PATHWAY ; PHOSPHORYLATION
英文摘要: The Wnt/beta-catenin signaling pathway has a crucial role in embryonic development, stem cell maintenance and human disease. By screening a synthetic chemical library of lycorine derivatives, we identified 4-ethyl-5-methyl-5,6-dihydro-[1,3]dioxolo[4,5-j]phenanthridine (HLY78) as an activator of the Wnt/beta-catenin signaling pathway, which acts in a Wnt ligand-dependent manner. HLY78 targets the DIX domain of Axin and potentiates the Axin-LRP6 association, thus promoting LRP6 phosphorylation and Wnt signaling transduction. Moreover, we identified the critical residues on Axin for HLY78 binding and showed that HLY78 may weaken the autoinhibition of Axin. In addition, HLY78 acts synergistically with Wnt in the embryonic development of zebrafish and increases the expression of the conserved hematopoietic stem cell (HSC) markers, runx1 and cmyb, in zebrafish embryos. Collectively, our study not only provides new insights into the regulation of the Wnt/beta-catenin signaling pathway by a Wnt-specific small molecule but also will facilitate therapeutic applications, such as HSC expansion.
出版日期: 2013-09-01
卷号: 9, 期号:9, 页码:579-U82
语种: 英语
收录类别: SCI
学科分类: Biochemistry & Molecular Biology
ISSN号: 1552-4450
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/16687
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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作者单位: 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol, Shanghai, Peoples R China

Recommended Citation:
Wang, Sheng; Yin, Junlin; Chen, Duozhi; Nie, Fen; Song, Xiaomin; Fei, Cong; Miao, Haofei; Jing, Changbin; Ma, Wenjing; Wang, Lei; Xie, Sichun; Li, Chen; Zeng, Rong; Pan, Weijun; Hao, Xiaojiang; Li, Lin.Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction,NATURE CHEMICAL BIOLOGY,2013,9(9):579-U82
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