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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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) |
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mitogen-activated protein kinase dual-specificity phosphatase MAP kinase phosphatase sex differences metabolic syndromes cancer Biology (General) QH301-705.5 Chemistry QD1-999 |
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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 |
_version_ |
1718432193309573120 |