PUBLICATION
Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization of beta-catenin-TCF interaction
- Authors
- Gan, X.Q., Wang, J.Y., Xi, Y., Wu, Z.L., Li, Y.P., and Li, L.
- ID
- ZDB-PUB-080326-27
- Date
- 2008
- Source
- The Journal of cell biology 180(6): 1087-1100 (Journal)
- Registered Authors
- Li, Lin
- Keywords
- none
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/genetics
- Adaptor Proteins, Signal Transducing/metabolism*
- Animals
- Cell Line
- Cell Line, Tumor
- Cell Nucleus/genetics
- Cell Nucleus/metabolism*
- Down-Regulation/genetics
- Gene Expression Regulation/genetics
- Humans
- Macromolecular Substances/metabolism
- Phosphoproteins/genetics
- Phosphoproteins/metabolism*
- Promoter Regions, Genetic/genetics
- Proto-Oncogene Proteins c-jun/genetics
- Proto-Oncogene Proteins c-jun/metabolism*
- Regulatory Elements, Transcriptional/genetics
- Signal Transduction/genetics
- TCF Transcription Factors/genetics
- TCF Transcription Factors/metabolism*
- Transcription Factor 7-Like 2 Protein
- Transcription, Genetic/genetics
- Wnt Proteins/genetics*
- Wnt Proteins/metabolism
- Zebrafish
- beta Catenin/genetics
- beta Catenin/metabolism*
- PubMed
- 18347071 Full text @ J. Cell Biol.
Citation
Gan, X.Q., Wang, J.Y., Xi, Y., Wu, Z.L., Li, Y.P., and Li, L. (2008) Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization of beta-catenin-TCF interaction. The Journal of cell biology. 180(6):1087-1100.
Abstract
In canonical Wnt signaling, Dishevelled (Dvl) is a critical cytoplasmic regulator that releases beta-catenin from degradation. Here, we find that Dvl and c-Jun form a complex with beta-catenin-T-cell factor 4 (TCF-4) on the promoter of Wnt target genes and regulate gene transcription. The complex forms via two interactions of nuclear Dvl with c-Jun and beta-catenin, respectively, both of which bind to TCF. Disrupting the interaction of Dvl with either c-Jun or beta-catenin suppresses canonical Wnt signaling-stimulated transcription, and the reduction of Dvl diminished beta-catenin-TCF-4 association on Wnt target gene promoters in vivo. Expression of a TCF-Dvl fusion protein largely rescued the c-Jun knockdown Wnt signaling deficiency in mammalian cells and zebrafish. Thus, we confirm that c-Jun functions in canonical Wnt signaling and show that c-Jun functions as a scaffold in the bet Expression of a TCF-Dvl fusion protein largely rescued the c-Jun knockdown Wnt signaling deficiency in mammalian cells and zebrafish. Thus, we cona-catenin-TCFs transcription complex bridging Dvl to TCF. Our results reveal a mechanism by which nuclear Dvl cooperates with c-Jun to regulate gene transcription stimulated by the canonical Wnt signaling pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping