Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction
文献类型：期刊论文
| 作者 | Wang, S; Yin, JL; Chen, DZ; Nie, F; Song, XM; Fei, C; Miao, HF; Jing, CB; Ma, WJ; Wang, L |
| 刊名 | NATURE CHEMICAL BIOLOGY
 |
| 出版日期 | 2013 |
| 卷号 | 9期号:9页码:579-U82 |
| 通讯作者 | Hao, 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 |
| 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. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | GLYCOGEN-SYNTHASE KINASE-3 ; BETA-CATENIN ; NEGATIVE REGULATOR ; DIX DOMAIN ; STEM-CELLS ; IN-VIVO ; AXIN ; ACTIVATION ; PATHWAY ; PHOSPHORYLATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000323417500010 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/429]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Wang, S,Yin, JL,Chen, DZ,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, S.,Yin, JL.,Chen, DZ.,Nie, F.,Song, XM.,...&Li, L.(2013).Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction.NATURE CHEMICAL BIOLOGY,9(9),579-U82. |
| MLA | Wang, S,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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