The regulation of oncogenic Ras/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs)

Seminars in Cell & Developmental Biology
Andrew M Kidger, S M Keyse

Abstract

Dual-specificity MAP kinase (MAPK) phosphatases (MKPs or DUSPs) are well-established negative regulators of MAPK signalling in mammalian cells and tissues. By virtue of their differential subcellular localisation and ability to specifically recognise, dephosphorylate and inactivate different MAPK isoforms, they are key spatiotemporal regulators of pathway activity. Furthermore, as they are transcriptionally regulated as downstream targets of MAPK signalling they can either act as classical negative feedback regulators or mediate cross talk between distinct MAPK pathways. Because MAPKs and particularly Ras/ERK signalling are implicated in cancer initiation and development, the observation that MKPs are abnormally regulated in human tumours has been interpreted as evidence that these enzymes can either suppress or promote carcinogenesis. However, definitive evidence of such roles has been lacking. Here we review recent work based on the use of mouse models, biochemical studies and clinical data that demonstrate key roles for MKPs in modulating the oncogenic potential of Ras/ERK signalling and also indicate that these enzymes may play a role in the response of tumours to certain anticancer drugs. Overall, this work reinforces the ...Continue Reading

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Citations

Jul 17, 2016·Seminars in Cell & Developmental Biology·Bingying ZhouAdrienne D Cox
Aug 31, 2016·Journal of Molecular and Cellular Cardiology·Ruijie Liu, Jeffery D Molkentin
Oct 16, 2016·Journal of Cellular Physiology·Luigi SapioSilvio Naviglio
Jun 24, 2017·Cancer Letters·Malcolm Brock, Yuping Mei
Sep 14, 2017·International Journal of Molecular Sciences·Noopur BhoreYung-Feng Liao
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Oct 15, 2019·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Chen ChenQing Lan
Feb 16, 2018·Development·Maria A MissinatoMichael Tsang
Oct 17, 2019·Biomolecules·Wisurumuni Arachchilage Hasitha Maduranga KarunarathneGi-Young Kim
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Jun 14, 2019·Molecular Carcinogenesis·Rachel M SammonsKevin N Dalby

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Methods Mentioned

BETA
gene knockout
xenograft
exome
biopsies

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