Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction

	Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction
	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
	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
内容类型	期刊论文
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.