PUBLICATION
Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling by promoting TCF/β-catenin transcriptional activity
- Authors
- He, X., Zhang, W., Yan, C., Nie, F., Li, C., Liu, X., Fei, C., Li, S., Song, X., Jia, Y., Zeng, R., Wu, D., Pan, W., Hao, X., Li, L.
- ID
- ZDB-PUB-170419-3
- Date
- 2017
- Source
- Cell discovery 3: 17003 (Journal)
- Registered Authors
- Jia, Yingying, Li, Lin, Nie, Fen, Pan, Weijun
- Keywords
- CARF, NC043, Wnt signaling, chemical biology, small molecule, Haematopoietic stem cells, Morphogen signalling, Proteomics
- MeSH Terms
- none
- PubMed
- 28417011 Full text @ Cell Discov
Citation
He, X., Zhang, W., Yan, C., Nie, F., Li, C., Liu, X., Fei, C., Li, S., Song, X., Jia, Y., Zeng, R., Wu, D., Pan, W., Hao, X., Li, L. (2017) Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling by promoting TCF/β-catenin transcriptional activity. Cell discovery. 3:17003.
Abstract
Wnt/β-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/β-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-β-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/β-catenin signal transduction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping