DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases

Mitogen-activated protein kinases (MAPKs) are essential for proper cell functioning as they regulate many molecular effectors. Careful regulation of MAPKs is therefore required to avoid MAPK pathway dysfunctions and pathologies. The mammalian genome encodes about 200 phosphatases, many of which deph...

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Autores principales: Fatma Zohra Khoubai, Christophe F. Grosset
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:a1618db3771d4ce3a0cf359094655b6e2021-11-11T16:59:59ZDUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases10.3390/ijms2221115381422-00671661-6596https://doaj.org/article/a1618db3771d4ce3a0cf359094655b6e2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11538https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mitogen-activated protein kinases (MAPKs) are essential for proper cell functioning as they regulate many molecular effectors. Careful regulation of MAPKs is therefore required to avoid MAPK pathway dysfunctions and pathologies. The mammalian genome encodes about 200 phosphatases, many of which dephosphorylate the MAPKs and bring them back to an inactive state. In this review, we focus on the normal and pathological functions of dual-specificity phosphatase 9 (<i>DUSP9</i>)/MAP kinase phosphatases-4 (MKP-4). This cytoplasmic phosphatase, which belongs to the threonine/tyrosine dual-specific phosphatase family and was first described in 1997, is known to dephosphorylate ERK1/2, p38, JNK and ASK1, and thereby to control various MAPK pathway cascades. As a consequence, <i>DUSP9</i> plays a major role in human pathologies and more specifically in cardiac dysfunction, liver metabolic syndromes, diabetes, obesity and cancer including drug response and cell stemness. Here, we recapitulate the mechanism of action of <i>DUSP9</i> in the cell, its levels of regulation and its roles in the most frequent human diseases, and discuss its potential as a therapeutic target.Fatma Zohra KhoubaiChristophe F. GrossetMDPI AGarticlemitogen-activated protein kinasedual-specificity phosphataseMAP kinase phosphatasesex differencesmetabolic syndromescancerBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11538, p 11538 (2021)
institution DOAJ
collection DOAJ
language EN
topic mitogen-activated protein kinase
dual-specificity phosphatase
MAP kinase phosphatase
sex differences
metabolic syndromes
cancer
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle mitogen-activated protein kinase
dual-specificity phosphatase
MAP kinase phosphatase
sex differences
metabolic syndromes
cancer
Biology (General)
QH301-705.5
Chemistry
QD1-999
Fatma Zohra Khoubai
Christophe F. Grosset
DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases
description Mitogen-activated protein kinases (MAPKs) are essential for proper cell functioning as they regulate many molecular effectors. Careful regulation of MAPKs is therefore required to avoid MAPK pathway dysfunctions and pathologies. The mammalian genome encodes about 200 phosphatases, many of which dephosphorylate the MAPKs and bring them back to an inactive state. In this review, we focus on the normal and pathological functions of dual-specificity phosphatase 9 (<i>DUSP9</i>)/MAP kinase phosphatases-4 (MKP-4). This cytoplasmic phosphatase, which belongs to the threonine/tyrosine dual-specific phosphatase family and was first described in 1997, is known to dephosphorylate ERK1/2, p38, JNK and ASK1, and thereby to control various MAPK pathway cascades. As a consequence, <i>DUSP9</i> plays a major role in human pathologies and more specifically in cardiac dysfunction, liver metabolic syndromes, diabetes, obesity and cancer including drug response and cell stemness. Here, we recapitulate the mechanism of action of <i>DUSP9</i> in the cell, its levels of regulation and its roles in the most frequent human diseases, and discuss its potential as a therapeutic target.
format article
author Fatma Zohra Khoubai
Christophe F. Grosset
author_facet Fatma Zohra Khoubai
Christophe F. Grosset
author_sort Fatma Zohra Khoubai
title DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases
title_short DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases
title_full DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases
title_fullStr DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases
title_full_unstemmed DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases
title_sort dusp9, a dual-specificity phosphatase with a key role in cell biology and human diseases
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/a1618db3771d4ce3a0cf359094655b6e
work_keys_str_mv AT fatmazohrakhoubai dusp9adualspecificityphosphatasewithakeyroleincellbiologyandhumandiseases
AT christophefgrosset dusp9adualspecificityphosphatasewithakeyroleincellbiologyandhumandiseases
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