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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Auteurs principaux:	Fatma Zohra Khoubai, Christophe F. Grosset
Format:	article
Langue:	EN
Publié:	MDPI AG 2021
Sujets:	mitogen-activated protein kinase dual-specificity phosphatase MAP kinase phosphatase sex differences metabolic syndromes cancer Biology (General) QH301-705.5 Chemistry QD1-999
Accès en ligne:	https://doaj.org/article/a1618db3771d4ce3a0cf359094655b6e
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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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DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases

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