| Autor: |
Wang S; 1] State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. [2]., Yin J, Chen D, Nie F, Song X, Fei C, Miao H, Jing C, Ma W, Wang L, Xie S, Li C, Zeng R, Pan W, Hao X, Li L |
| Jazyk: |
angličtina |
| Zdroj: |
Nature chemical biology [Nat Chem Biol] 2013 Sep; Vol. 9 (9), pp. 579-85. Date of Electronic Publication: 2013 Jul 28. |
| DOI: |
10.1038/nchembio.1309 |
| Abstrakt: |
The Wnt/β-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/β-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/β-catenin signaling pathway by a Wnt-specific small molecule but also will facilitate therapeutic applications, such as HSC expansion. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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