Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling by promoting TCF/beta-catenin transcriptional activity
He, Xiaoli1; Zhang, Wenjuan2,3; Yan, Chen4; Nie, Fen1; Li, Chen5; Liu, Xiaofen2,3; Fei, Cong1; Li, Shengdi5; Song, Xiaomin1; Jia, Yingying1; Zeng, Rong; Wu, Dianqing6,7; Pan, Weijun2,3; Hao, Xiaojiang4; Li, Lin1
2017-01-31
发表期刊CELL DISCOVERY
ISSN2056-5968
卷号3页码:17003
摘要Wnt/beta-catenin signaling regulates multiple biological processes and aberration of this pathway is frequently observed in human cancers. Previously, we uncovered NC043 as a small-molecule inhibitor of Wnt/beta-catenin signaling. Here, we identified CARF as the cellular target of NC043. We found that NC043 binds directly to CARF through forming a covalent bond with the Cys-516 residue of CARF. Further study revealed that CARF interacts with Dvl, which potentiates the Dvl-c-Jun-beta-catenin-TCF transcriptional complex and thus promotes Wnt signaling activation. NC043 could disrupt the interaction between CARF and Dvl, thereby impairing Wnt signal transduction. In line with this, knockdown of CARF in zebrafish leads to impairment of embryonic development, hematopoietic stem cell generation and caudal fin regeneration. Collectively, we identified CARF as the cellular target of NC043 and revealed CARF as a positive regulator of Wnt/beta-catenin signal transduction.
关键词Carf Chemical Biology Nc043 Small Molecule Wnt Signaling
语种英语
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/60352
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, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol, Shanghai, Peoples R China
6.Yale Sch Med, Vasc Biol & Therapeut Program, New Haven, CT USA
7.Yale Sch Med, Dept Pharmacol, New Haven, CT USA
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He, Xiaoli,Zhang, Wenjuan,Yan, Chen,et al. Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling by promoting TCF/beta-catenin transcriptional activity[J]. CELL DISCOVERY,2017,3:17003.
APA He, Xiaoli.,Zhang, Wenjuan.,Yan, Chen.,Nie, Fen.,Li, Chen.,...&Li, Lin.(2017).Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling by promoting TCF/beta-catenin transcriptional activity.CELL DISCOVERY,3,17003.
MLA He, Xiaoli,et al."Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling by promoting TCF/beta-catenin transcriptional activity".CELL DISCOVERY 3(2017):17003.
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