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
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
Figures
Figure Gallery (2 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cas009
    Indel
    ia4TgTransgenic Insertion
      y206TgTransgenic Insertion
        zdf1
          Point Mutation
          zf169TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            cdkn2aipCRISPR1-cdkn2aipCRISPR
            cdkn2aipMO1-cdkn2aipMRPHLNO
            tp53MO7-tp53MRPHLNO
            wnt8aMO1-wnt8aMRPHLNO
            wnt8aMO2-wnt8aMRPHLNO
            1 - 5 of 5
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            Fish
            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            GFPEFGGFP
            mCherryEFGmCherry
            1 - 3 of 3
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            Mapping
            No data available