Regulation of Wnt/PCP signaling through p97/VCP-KBTBD7-mediated Vangl ubiquitination and endoplasmic reticulum-associated degradation

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Di Feng
  • Jin Wang
  • Wei Yang
  • Xiaochen Lin
  • Fangzi Zha
  • Xiaolu Wang
  • Luyao Ma
  • Nga Ting Choi
  • Yusuke Mii
  • Shinji Takada
  • Michael S. Y. Huen
  • Yusong Guo
  • Bo Gao

Detail(s)

Original languageEnglish
Article numbereabg2099
Journal / PublicationScience Advances
Volume7
Issue number20
Online published14 May 2021
Publication statusPublished - May 2021

Link(s)

Abstract

The four-pass transmembrane proteins Vangl1 and Vangl2, are dedicated core components of Wnt/planar cell polarity (Wnt/PCP) signaling that critically regulate polarized cell behaviors in many morphological and physiological processes. Here, we found that the abundance of Vangl proteins is tightly controlled by the ubiquitin-proteasome system through endoplasmic reticulum-associated degradation (ERAD). The key ERAD component p97/VCP directly binds to Vangl at a highly conserved VCP-interacting motif and recruits the E3 ligase KBTBD7 via its UBA-UBX adaptors to promote Vangl ubiquitination and ERAD. We found that Wnt5a/CK1 prevents Vangl ubiquitination and ERAD by inducing Vangl phosphorylation, which facilitates Vangl export from the ER to the plasma membrane. We also provide in vivo evidence that KBTBD7 regulates convergent extension during zebrafish gastrulation and functions as a tumor suppressor in breast cancer by promoting Vangl degradation. Our findings reveal a previously unknown regulatory mechanism of Wnt/PCP signaling through the p97/VCPKBTBD7- mediated ERAD pathway.

Research Area(s)

Citation Format(s)

Regulation of Wnt/PCP signaling through p97/VCP-KBTBD7-mediated Vangl ubiquitination and endoplasmic reticulum-associated degradation. / Feng, Di; Wang, Jin; Yang, Wei; Li, Jingyu; Lin, Xiaochen; Zha, Fangzi; Wang, Xiaolu; Ma, Luyao; Choi, Nga Ting; Mii, Yusuke; Takada, Shinji; Huen, Michael S. Y.; Guo, Yusong; Zhang, Liang; Gao, Bo.

In: Science Advances, Vol. 7, No. 20, eabg2099, 05.2021.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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