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Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers

The Wnt signaling pathway plays important roles in embryonic development, homeostatic processes, cell differentiation, cell polarity, cell proliferation, and cell migration via the β-catenin binding of Wnt target genes. Dysregulation of Wnt signaling is associated with various diseases such as cance...

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Autores principales: Park, Hong-Beom, Kim, Ju-Won, Baek, Kwang-Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311976/
https://www.ncbi.nlm.nih.gov/pubmed/32486158
http://dx.doi.org/10.3390/ijms21113904
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author Park, Hong-Beom
Kim, Ju-Won
Baek, Kwang-Hyun
author_facet Park, Hong-Beom
Kim, Ju-Won
Baek, Kwang-Hyun
author_sort Park, Hong-Beom
collection PubMed
description The Wnt signaling pathway plays important roles in embryonic development, homeostatic processes, cell differentiation, cell polarity, cell proliferation, and cell migration via the β-catenin binding of Wnt target genes. Dysregulation of Wnt signaling is associated with various diseases such as cancer, aging, Alzheimer’s disease, metabolic disease, and pigmentation disorders. Numerous studies entailing the Wnt signaling pathway have been conducted for various cancers. Diverse signaling factors mediate the up- or down-regulation of Wnt signaling through post-translational modifications (PTMs), and aberrant regulation is associated with several different malignancies in humans. Of the numerous PTMs involved, most Wnt signaling factors are regulated by ubiquitination and deubiquitination. Ubiquitination by E3 ligase attaches ubiquitins to target proteins and usually induces proteasomal degradation of Wnt signaling factors such as β-catenin, Axin, GSK3, and Dvl. Conversely, deubiquitination induced by the deubiquitinating enzymes (DUBs) detaches the ubiquitins and modulates the stability of signaling factors. In this review, we discuss the effects of ubiquitination and deubiquitination on the Wnt signaling pathway, and the inhibitors of DUBs that can be applied for cancer therapeutic strategies.
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spelling pubmed-73119762020-06-25 Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers Park, Hong-Beom Kim, Ju-Won Baek, Kwang-Hyun Int J Mol Sci Review The Wnt signaling pathway plays important roles in embryonic development, homeostatic processes, cell differentiation, cell polarity, cell proliferation, and cell migration via the β-catenin binding of Wnt target genes. Dysregulation of Wnt signaling is associated with various diseases such as cancer, aging, Alzheimer’s disease, metabolic disease, and pigmentation disorders. Numerous studies entailing the Wnt signaling pathway have been conducted for various cancers. Diverse signaling factors mediate the up- or down-regulation of Wnt signaling through post-translational modifications (PTMs), and aberrant regulation is associated with several different malignancies in humans. Of the numerous PTMs involved, most Wnt signaling factors are regulated by ubiquitination and deubiquitination. Ubiquitination by E3 ligase attaches ubiquitins to target proteins and usually induces proteasomal degradation of Wnt signaling factors such as β-catenin, Axin, GSK3, and Dvl. Conversely, deubiquitination induced by the deubiquitinating enzymes (DUBs) detaches the ubiquitins and modulates the stability of signaling factors. In this review, we discuss the effects of ubiquitination and deubiquitination on the Wnt signaling pathway, and the inhibitors of DUBs that can be applied for cancer therapeutic strategies. MDPI 2020-05-30 /pmc/articles/PMC7311976/ /pubmed/32486158 http://dx.doi.org/10.3390/ijms21113904 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Park, Hong-Beom
Kim, Ju-Won
Baek, Kwang-Hyun
Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers
title Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers
title_full Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers
title_fullStr Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers
title_full_unstemmed Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers
title_short Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers
title_sort regulation of wnt signaling through ubiquitination and deubiquitination in cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311976/
https://www.ncbi.nlm.nih.gov/pubmed/32486158
http://dx.doi.org/10.3390/ijms21113904
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