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

TitleRegulation of Wnt/PCP signaling through p97/VCP-KBTBD7-mediated Vangl ubiquitination and endoplasmic reticulum-associated degradation
Authors
Issue Date2021
PublisherAmerican Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/
Citation
Science Advances, 2021, v. 7 n. 20, p. article no. eabg2099 How to Cite?
AbstractThe 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/VCP-KBTBD7-mediated ERAD pathway.
Persistent Identifierhttp://hdl.handle.net/10722/304897
ISSN
2023 Impact Factor: 11.7
2023 SCImago Journal Rankings: 4.483
PubMed Central ID
ISI Accession Number ID
Grants

 

DC FieldValueLanguage
dc.contributor.authorFeng, D-
dc.contributor.authorWang, J-
dc.contributor.authorYang, W-
dc.contributor.authorLi, J-
dc.contributor.authorLin, X-
dc.contributor.authorZha, F-
dc.contributor.authorWang, X-
dc.contributor.authorMa, L-
dc.contributor.authorChoi, NT-
dc.contributor.authorMii, Y-
dc.contributor.authorTakada, S-
dc.contributor.authorHuen, MSY-
dc.contributor.authorGuo, Y-
dc.contributor.authorZhang, L-
dc.contributor.authorGao, B-
dc.date.accessioned2021-10-05T02:36:47Z-
dc.date.available2021-10-05T02:36:47Z-
dc.date.issued2021-
dc.identifier.citationScience Advances, 2021, v. 7 n. 20, p. article no. eabg2099-
dc.identifier.issn2375-2548-
dc.identifier.urihttp://hdl.handle.net/10722/304897-
dc.description.abstractThe 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/VCP-KBTBD7-mediated ERAD pathway.-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/-
dc.relation.ispartofScience Advances-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleRegulation of Wnt/PCP signaling through p97/VCP-KBTBD7-mediated Vangl ubiquitination and endoplasmic reticulum-associated degradation-
dc.typeArticle-
dc.identifier.emailFeng, D: fengdi90@hku.hk-
dc.identifier.emailLin, X: xlinal92@hku.hk-
dc.identifier.emailChoi, NT: vntchoi@hku.hk-
dc.identifier.emailHuen, MSY: huen.michael@hku.hk-
dc.identifier.emailGao, B: gaobo@hku.hk-
dc.identifier.authorityHuen, MSY=rp01336-
dc.identifier.authorityGao, B=rp02012-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1126/sciadv.abg2099-
dc.identifier.pmid33990333-
dc.identifier.pmcidPMC8121430-
dc.identifier.scopuseid_2-s2.0-85105938988-
dc.identifier.hkuros325774-
dc.identifier.volume7-
dc.identifier.issue20-
dc.identifier.spagearticle no. eabg2099-
dc.identifier.epagearticle no. eabg2099-
dc.identifier.isiWOS:000652258100033-
dc.publisher.placeUnited States-
dc.relation.projectRegulation of non-canonical Wnt/PCP signaling by Vangl2 phosphorylation-

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