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Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability

Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of dura...

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Autores principales: Chen, Hsueh-Fen, Chuang, Huai-Chia, Tan, Tse-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600639/
https://www.ncbi.nlm.nih.gov/pubmed/31151270
http://dx.doi.org/10.3390/ijms20112668
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author Chen, Hsueh-Fen
Chuang, Huai-Chia
Tan, Tse-Hua
author_facet Chen, Hsueh-Fen
Chuang, Huai-Chia
Tan, Tse-Hua
author_sort Chen, Hsueh-Fen
collection PubMed
description Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications.
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spelling pubmed-66006392019-07-16 Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability Chen, Hsueh-Fen Chuang, Huai-Chia Tan, Tse-Hua Int J Mol Sci Review Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications. MDPI 2019-05-30 /pmc/articles/PMC6600639/ /pubmed/31151270 http://dx.doi.org/10.3390/ijms20112668 Text en © 2019 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
Chen, Hsueh-Fen
Chuang, Huai-Chia
Tan, Tse-Hua
Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
title Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
title_full Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
title_fullStr Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
title_full_unstemmed Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
title_short Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
title_sort regulation of dual-specificity phosphatase (dusp) ubiquitination and protein stability
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600639/
https://www.ncbi.nlm.nih.gov/pubmed/31151270
http://dx.doi.org/10.3390/ijms20112668
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