Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction
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; Hao, Xiaojiang2; Li, Lin1
2013-09-01
发表期刊NATURE CHEMICAL BIOLOGY
ISSN1552-4450
卷号9期号:9页码:579-U82
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.
关键词Glycogen-synthase Kinase-3 Beta-catenin Negative Regulator Dix Domain Stem-cells In-vivo Axin Activation Pathway Phosphorylation
资助信息Ministry of Science and Technology of China [2010CB912100, 2011CB966300, 2013CB910900]; National Natural Science Foundation of China [30930052, 31230044, 30830114]
学科领域Biochemistry & Molecular Biology
收录类别SCI
语种英语
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:000323417500010
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/16687
专题植物化学与西部植物资源持续利用国家重点实验室
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
推荐引用方式
GB/T 7714
Wang, Sheng,Yin, Junlin,Chen, Duozhi,et al. Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction[J]. NATURE CHEMICAL BIOLOGY,2013,9(9):579-U82.
APA Wang, Sheng.,Yin, Junlin.,Chen, Duozhi.,Nie, Fen.,Song, Xiaomin.,...&Li, Lin.(2013).Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction.NATURE CHEMICAL BIOLOGY,9(9),579-U82.
MLA Wang, Sheng,et al."Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction".NATURE CHEMICAL BIOLOGY 9.9(2013):579-U82.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
Wang-2013-Small-mole(1157KB) 开放获取--请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Wang, Sheng]的文章
[Yin, Junlin]的文章
[Chen, Duozhi]的文章
百度学术
百度学术中相似的文章
[Wang, Sheng]的文章
[Yin, Junlin]的文章
[Chen, Duozhi]的文章
必应学术
必应学术中相似的文章
[Wang, Sheng]的文章
[Yin, Junlin]的文章
[Chen, Duozhi]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。