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WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein

WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a member of C2-WW-HECT E3 ligase family. Although it may execute carcinostatic actions in some scenarios, WWP1 functions as an oncoprotein under most circumstances. Here, we comprehensively review reports on regulation of WWP1 and its role...

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Autores principales: Kuang, Linghan, Jiang, Yunhui, Li, Chenghua, Jiang, Yongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545989/
https://www.ncbi.nlm.nih.gov/pubmed/34712671
http://dx.doi.org/10.3389/fcell.2021.757493
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author Kuang, Linghan
Jiang, Yunhui
Li, Chenghua
Jiang, Yongmei
author_facet Kuang, Linghan
Jiang, Yunhui
Li, Chenghua
Jiang, Yongmei
author_sort Kuang, Linghan
collection PubMed
description WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a member of C2-WW-HECT E3 ligase family. Although it may execute carcinostatic actions in some scenarios, WWP1 functions as an oncoprotein under most circumstances. Here, we comprehensively review reports on regulation of WWP1 and its roles in tumorigenesis. We summarize the WWP1-mediated ubiquitinations of diverse proteins and the signaling pathways they involved, as well as the mechanisms how they affect cancer formation and progression. According to our analysis of database, in combination with previous reports, we come to a conclusion that WWP1 expression is augmented in various cancers. Gene amplification, as well as expression regulation mediated by molecules such as non-coding RNAs, may account for the increased mRNA level of WWP1. Regulation of enzymatic activity is another important facet to upregulate WWP1-mediated ubiquitinations. Based on the published data, we conclude that WWP1 employs interactions between multiple domains to autoinhibit its polyubiquitination activity in a steady state. Association of some substrates can partially release certain autoinhibition-related domains and make WWP1 have a moderate activity of polyubiquitination. Some cancer-related mutations can fully disrupt the inhibitory interactions and make WWP1 hyperactive. High expression level or hyperactivation of WWP1 may abnormally enhance polyubiquitinations of some oncoproteins or tumor suppressors, such as ΔNp63α, PTEN and p27, and ultimately promote cell proliferation, survival, migration and invasion in tumorigenesis. Given the dysregulation and oncogenic functions of WWP1 in some cancer types, it is promising to explore some therapeutic inhibitors to tune down its activity.
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spelling pubmed-85459892021-10-27 WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein Kuang, Linghan Jiang, Yunhui Li, Chenghua Jiang, Yongmei Front Cell Dev Biol Cell and Developmental Biology WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a member of C2-WW-HECT E3 ligase family. Although it may execute carcinostatic actions in some scenarios, WWP1 functions as an oncoprotein under most circumstances. Here, we comprehensively review reports on regulation of WWP1 and its roles in tumorigenesis. We summarize the WWP1-mediated ubiquitinations of diverse proteins and the signaling pathways they involved, as well as the mechanisms how they affect cancer formation and progression. According to our analysis of database, in combination with previous reports, we come to a conclusion that WWP1 expression is augmented in various cancers. Gene amplification, as well as expression regulation mediated by molecules such as non-coding RNAs, may account for the increased mRNA level of WWP1. Regulation of enzymatic activity is another important facet to upregulate WWP1-mediated ubiquitinations. Based on the published data, we conclude that WWP1 employs interactions between multiple domains to autoinhibit its polyubiquitination activity in a steady state. Association of some substrates can partially release certain autoinhibition-related domains and make WWP1 have a moderate activity of polyubiquitination. Some cancer-related mutations can fully disrupt the inhibitory interactions and make WWP1 hyperactive. High expression level or hyperactivation of WWP1 may abnormally enhance polyubiquitinations of some oncoproteins or tumor suppressors, such as ΔNp63α, PTEN and p27, and ultimately promote cell proliferation, survival, migration and invasion in tumorigenesis. Given the dysregulation and oncogenic functions of WWP1 in some cancer types, it is promising to explore some therapeutic inhibitors to tune down its activity. Frontiers Media S.A. 2021-10-12 /pmc/articles/PMC8545989/ /pubmed/34712671 http://dx.doi.org/10.3389/fcell.2021.757493 Text en Copyright © 2021 Kuang, Jiang, Li and Jiang. 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 Cell and Developmental Biology
Kuang, Linghan
Jiang, Yunhui
Li, Chenghua
Jiang, Yongmei
WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein
title WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein
title_full WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein
title_fullStr WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein
title_full_unstemmed WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein
title_short WW Domain-Containing E3 Ubiquitin Protein Ligase 1: A Self-Disciplined Oncoprotein
title_sort ww domain-containing e3 ubiquitin protein ligase 1: a self-disciplined oncoprotein
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545989/
https://www.ncbi.nlm.nih.gov/pubmed/34712671
http://dx.doi.org/10.3389/fcell.2021.757493
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