2. Academic Validation
  3. VBP1 modulates Wnt/β-catenin signaling by mediating the stability of the transcription factors TCF/LEFs

VBP1 modulates Wnt/β-catenin signaling by mediating the stability of the transcription factors TCF/LEFs

  • J Biol Chem. 2020 Dec 4;295(49):16826-16839. doi: 10.1074/jbc.RA120.015282.
Haifeng Zhang 1,  Xiaozhi Rong 2,  Caixia Wang 1,  Yunzhang Liu 1,  Ling Lu 1,  Yun Li 1,  Chengtian Zhao 3,  Jianfeng Zhou 4
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China.
  • 2 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address: rongxiaozhi@ouc.edu.cn.
  • 3 Institute of Evolution and Marine Biodiversity and College of Marine Biology, Ocean University of China, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China.
  • 4 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address: jfzhou@ouc.edu.cn.
PMID: 32989053 DOI: 10.1074/jbc.RA120.015282
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 and 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 provide mechanistic insights into the roles of VBP1 in controlling TCF/LEFs protein stability and regulating Wnt/β-catenin signaling pathway activity.

Keywords

T-cell factor (TCF); TCF/LEF; VBP1; Wnt signaling; Wnt/β-catenin signaling; cell biology; pVHL; transcription factor; zebrafish.

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