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The Post-translational Modifications of Smurf2 in TGF-β Signaling

Smad ubiquitin regulatory factor 2 (Smurf2), an essential negative regulator of TGF-β signaling, ubiquitinates TGF-β receptors (TβRs) and Smad proteins, inducing their proteasomal degradation. Smurf2 plays crucial roles in regulating TGF-β signaling and maintaining normal cellular functions and tiss...

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Autores principales: Bai, Yangjinming, Ying, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358609/
https://www.ncbi.nlm.nih.gov/pubmed/32733916
http://dx.doi.org/10.3389/fmolb.2020.00128
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author Bai, Yangjinming
Ying, Ying
author_facet Bai, Yangjinming
Ying, Ying
author_sort Bai, Yangjinming
collection PubMed
description Smad ubiquitin regulatory factor 2 (Smurf2), an essential negative regulator of TGF-β signaling, ubiquitinates TGF-β receptors (TβRs) and Smad proteins, inducing their proteasomal degradation. Smurf2 plays crucial roles in regulating TGF-β signaling and maintaining normal cellular functions and tissue homeostasis; dysfunction of Smurf2 triggers abnormal TGF-β signaling in pathological states. Smurf2 has been reported as a potentially strong candidate for targeting therapies for related diseases. Recent work has begun to focus on the regulation of Smurf2 itself, and emerging evidence indicates that Smurf2 is regulated by post-translational modifications (PTMs) mechanisms. These mechanisms predominantly regulate the expression level and E3 ligase activity of Smurf2, strongly suggesting that this protein contributes to complicated roles under multiple pathophysiological conditions. In this review, we cover some significant and novel mechanisms of the PTMs that potentially control Smurf2 participation in TGF-β signaling, including ubiquitylation, SUMOylation, neddylation, phosphorylation, and methylation in order to provide a broad view of the depth and sophistication of Smurf2 function in TGF-β regulation, as well as perspectives for future therapeutic directions for its associated diseases.
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spelling pubmed-73586092020-07-29 The Post-translational Modifications of Smurf2 in TGF-β Signaling Bai, Yangjinming Ying, Ying Front Mol Biosci Molecular Biosciences Smad ubiquitin regulatory factor 2 (Smurf2), an essential negative regulator of TGF-β signaling, ubiquitinates TGF-β receptors (TβRs) and Smad proteins, inducing their proteasomal degradation. Smurf2 plays crucial roles in regulating TGF-β signaling and maintaining normal cellular functions and tissue homeostasis; dysfunction of Smurf2 triggers abnormal TGF-β signaling in pathological states. Smurf2 has been reported as a potentially strong candidate for targeting therapies for related diseases. Recent work has begun to focus on the regulation of Smurf2 itself, and emerging evidence indicates that Smurf2 is regulated by post-translational modifications (PTMs) mechanisms. These mechanisms predominantly regulate the expression level and E3 ligase activity of Smurf2, strongly suggesting that this protein contributes to complicated roles under multiple pathophysiological conditions. In this review, we cover some significant and novel mechanisms of the PTMs that potentially control Smurf2 participation in TGF-β signaling, including ubiquitylation, SUMOylation, neddylation, phosphorylation, and methylation in order to provide a broad view of the depth and sophistication of Smurf2 function in TGF-β regulation, as well as perspectives for future therapeutic directions for its associated diseases. Frontiers Media S.A. 2020-07-07 /pmc/articles/PMC7358609/ /pubmed/32733916 http://dx.doi.org/10.3389/fmolb.2020.00128 Text en Copyright © 2020 Bai and Ying. http://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 Molecular Biosciences
Bai, Yangjinming
Ying, Ying
The Post-translational Modifications of Smurf2 in TGF-β Signaling
title The Post-translational Modifications of Smurf2 in TGF-β Signaling
title_full The Post-translational Modifications of Smurf2 in TGF-β Signaling
title_fullStr The Post-translational Modifications of Smurf2 in TGF-β Signaling
title_full_unstemmed The Post-translational Modifications of Smurf2 in TGF-β Signaling
title_short The Post-translational Modifications of Smurf2 in TGF-β Signaling
title_sort post-translational modifications of smurf2 in tgf-β signaling
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358609/
https://www.ncbi.nlm.nih.gov/pubmed/32733916
http://dx.doi.org/10.3389/fmolb.2020.00128
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