ZFIN ID: ZDB-PUB-201002-203
VBP1 modulates Wnt/β-catenin signaling by mediating the stability of the transcription factors TCF/LEFs
Zhang, H., Rong, X., Wang, C., Liu, Y., Lu, L., Li, Y., Zhao, C., Zhou, J.
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.
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.