PUBLICATION
VBP1 modulates Wnt/β-catenin signaling by mediating the stability of the transcription factors TCF/LEFs
- Authors
- Zhang, H., Rong, X., Wang, C., Liu, Y., Lu, L., Li, Y., Zhao, C., Zhou, J.
- ID
- ZDB-PUB-201002-203
- Date
- 2020
- Source
- The Journal of biological chemistry 295(49): 16826-16839 (Journal)
- Registered Authors
- Rong, Xiaozhi, Wang, Caixia, Zhang, Haifeng, Zhao, Chengtian, Zhou, Jianfeng
- Keywords
- T-cell factor (TCF), TCF/LEF, VBP1, Wnt signaling, Wnt/β-catenin signaling, cell biology, pVHL, transcription factor, zebrafish
- MeSH Terms
-
- Animals
- Cell Line
- Cell Proliferation
- Cytoskeletal Proteins/antagonists & inhibitors
- Cytoskeletal Proteins/genetics
- Cytoskeletal Proteins/metabolism*
- Embryo, Nonmammalian/metabolism
- Humans
- Molecular Chaperones/antagonists & inhibitors
- Molecular Chaperones/genetics
- Molecular Chaperones/metabolism*
- Phosphorylation
- RNA Interference
- RNA, Small Interfering/metabolism
- TCF Transcription Factors/genetics
- TCF Transcription Factors/metabolism*
- Transcription Factor 7-Like 1 Protein/genetics
- Transcription Factor 7-Like 1 Protein/metabolism
- Transcription Factor 7-Like 2 Protein/genetics
- Transcription Factor 7-Like 2 Protein/metabolism
- Transcriptional Activation
- Wnt Proteins/genetics
- Wnt Proteins/metabolism
- Wnt Signaling Pathway*
- Zebrafish/growth & development
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- beta Catenin/genetics
- beta Catenin/metabolism
- PubMed
- 32989053 Full text @ J. Biol. Chem.
Citation
Zhang, H., Rong, X., Wang, C., Liu, Y., Lu, L., Li, Y., Zhao, C., Zhou, J. (2020) VBP1 modulates Wnt/β-catenin signaling by mediating the stability of the transcription factors TCF/LEFs. The Journal of biological chemistry. 295(49):16826-16839.
Abstract
The Wnt/β-catenin pathway is one of the major pathways that regulates embryonic development, adult homeostasis, and stem cell self-renewal. In this pathway, transcription factors T-cell factor/lymphoid enhancer factor (TCF/LEF), serve as a key switch to repress or activate Wnt target gene transcription by recruiting repressor molecules or interacting with the β-catenin effector, respectively. It has become evident that the protein stability of the TCF/LEF family members may play a critical role in controlling the activity of the Wnt/β-catenin signaling pathway. However, factors that regulate the stability of TCF/LEFs remain largely unknown. Here, we report that pVHL binding protein 1 (VBP1) regulates the Wnt/β-catenin signaling pathway by controlling the stability of TCF/LEFs. Surprisingly, we found that either overexpression or knockdown of VBP1 decreased Wnt/β-catenin signaling activity in both cultured cells and zebrafish embryos. Mechanistically, VBP1 directly binds to all four TCF/LEF family members and von Hippel-Lindau tumor suppressor protein (pVHL). Either overexpression or knockdown of VBP1 increases the association between TCF/LEFs and pVHL, and then decreases the protein levels of TCF/LEFs via proteasomal degradation. Together, our results provided mechanistic insights into the roles of VBP1 in controlling TCF/LEFs protein stability and regulating Wnt/β-catenin signaling pathway activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping