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SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway

Axin1 is a fundamental scaffolding protein of the destruction complex in the canonical Wnt signaling pathway, which plays a critical role in various biological processes. However, how Axin1 is regulated in the activation of the canonical Wnt signaling pathway remains elusive. Here, we report that Ax...

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Autores principales: Wang, Yuting, Yue, Jicheng, Xiao, Mingzhe, Lu, Xiaomei, Chin, Yuen Eugene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190513/
https://www.ncbi.nlm.nih.gov/pubmed/35707358
http://dx.doi.org/10.3389/fonc.2022.872444
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author Wang, Yuting
Yue, Jicheng
Xiao, Mingzhe
Lu, Xiaomei
Chin, Yuen Eugene
author_facet Wang, Yuting
Yue, Jicheng
Xiao, Mingzhe
Lu, Xiaomei
Chin, Yuen Eugene
author_sort Wang, Yuting
collection PubMed
description Axin1 is a fundamental scaffolding protein of the destruction complex in the canonical Wnt signaling pathway, which plays a critical role in various biological processes. However, how Axin1 is regulated in the activation of the canonical Wnt signaling pathway remains elusive. Here, we report that Axin1 is constitutively acetylated in resting cells. Upon stimulation with Wnt, SIRT4 translocates from mitochondria to the cytoplasm and catalyzes Axin1 deacetylation, thus turning off the destruction complex. In this process, Lys147, a residue in the RGS domain of Axin1, plays a key role. We proved that the Axin1-K147R mutant impairs the assembly of β-TrCP to the destruction complex, which leads to β-catenin accumulation even without Wnt stimulation. In summary, our work proposes a new model for better understanding the initial stage of the canonical Wnt signaling pathway in which SIRT4 translocates from mitochondria into the cytoplasm to deacetylate Axin1-K147 after Wnt stimulation, which results in reduced assembly of β-TrCP to the destruction complex.
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spelling pubmed-91905132022-06-14 SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway Wang, Yuting Yue, Jicheng Xiao, Mingzhe Lu, Xiaomei Chin, Yuen Eugene Front Oncol Oncology Axin1 is a fundamental scaffolding protein of the destruction complex in the canonical Wnt signaling pathway, which plays a critical role in various biological processes. However, how Axin1 is regulated in the activation of the canonical Wnt signaling pathway remains elusive. Here, we report that Axin1 is constitutively acetylated in resting cells. Upon stimulation with Wnt, SIRT4 translocates from mitochondria to the cytoplasm and catalyzes Axin1 deacetylation, thus turning off the destruction complex. In this process, Lys147, a residue in the RGS domain of Axin1, plays a key role. We proved that the Axin1-K147R mutant impairs the assembly of β-TrCP to the destruction complex, which leads to β-catenin accumulation even without Wnt stimulation. In summary, our work proposes a new model for better understanding the initial stage of the canonical Wnt signaling pathway in which SIRT4 translocates from mitochondria into the cytoplasm to deacetylate Axin1-K147 after Wnt stimulation, which results in reduced assembly of β-TrCP to the destruction complex. Frontiers Media S.A. 2022-05-30 /pmc/articles/PMC9190513/ /pubmed/35707358 http://dx.doi.org/10.3389/fonc.2022.872444 Text en Copyright © 2022 Wang, Yue, Xiao, Lu and Chin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Yuting
Yue, Jicheng
Xiao, Mingzhe
Lu, Xiaomei
Chin, Yuen Eugene
SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway
title SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway
title_full SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway
title_fullStr SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway
title_full_unstemmed SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway
title_short SIRT4-Catalyzed Deacetylation of Axin1 Modulates the Wnt/β-Catenin Signaling Pathway
title_sort sirt4-catalyzed deacetylation of axin1 modulates the wnt/β-catenin signaling pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190513/
https://www.ncbi.nlm.nih.gov/pubmed/35707358
http://dx.doi.org/10.3389/fonc.2022.872444
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