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
Corresponding AuthorHao, XJ (reprint author), Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Peoples R China. ; haoxj@mail.kib.ac.cn ; lli@sibs.ac.cn
2013-09-01
Source PublicationNATURE CHEMICAL BIOLOGY
ISSN1552-4450
Volume9Issue:9Pages:579-U82
AbstractThe 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.
KeywordGlycogen-synthase Kinase-3 Beta-catenin Negative Regulator Dix Domain Stem-cells In-vivo Axin Activation Pathway Phosphorylation
Subject AreaBiochemistry & Molecular Biology
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000323417500010
Citation statistics
Cited Times:42[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/16687
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.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
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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.
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