Abstract
The protein tyrosine phosphatase family (PTP) contains a group of dual-specificity phosphatases (DUSPs) that regulate the activivity of MAP kinases (MAPKs), which are key effectors in the control of cell growth and survival in physiological and pathological processes, including cancer. These phosphatases, named as MKP-DUSPs, include the MAPK phosphatases (MKPs) as well as a group of small-size atypical DUSPs structurally and functionally related to the MKPs. MKP-DUSPs, in most of the cases, are direct inactivators of MAPKs by dephosphorylation of both the Thr and the Tyr regulatory residues at the MAPKs catalytic loop. In some other cases, MKPDUSPs regulate the activity of MAPKs indirectly, acting through upstream MAPK pathways components. The active involvement of MKP-DUSPs in oncogenesis or resistance to cancer therapies is now well documented, making the search and validation of MKP-DUSPs inhibitors a prominent area in clinical cancer research. Here, we review the current knowledge on the role of MKP-DUSPs in human cancer, the status of the preclinical development and validation of specific MKP-DUSP inhibitors, and the potential of MKP-DUSPs as targets for anti-cancer drugs.
Keywords: Protein tyrosine phosphatases (PTPs), dual-specificity phosphatases (DUSPs), MAP kinase phosphatases (MKPs), inhibitors, anti-cancer agents, JNK1, VRK3, ERK1/2, dual specificity, LNCaP, PMA
Anti-Cancer Agents in Medicinal Chemistry
Title: Dual-Specificity MAP Kinase Phosphatases as Targets of Cancer Treatment
Volume: 11 Issue: 1
Author(s): Caroline Nunes-Xavier, Carlos Roma-Mateo, Pablo Rios, Celine Tarrega, Rocio Cejudo-Marin, Lydia Tabernero and Rafael Pulido
Affiliation:
Keywords: Protein tyrosine phosphatases (PTPs), dual-specificity phosphatases (DUSPs), MAP kinase phosphatases (MKPs), inhibitors, anti-cancer agents, JNK1, VRK3, ERK1/2, dual specificity, LNCaP, PMA
Abstract: The protein tyrosine phosphatase family (PTP) contains a group of dual-specificity phosphatases (DUSPs) that regulate the activivity of MAP kinases (MAPKs), which are key effectors in the control of cell growth and survival in physiological and pathological processes, including cancer. These phosphatases, named as MKP-DUSPs, include the MAPK phosphatases (MKPs) as well as a group of small-size atypical DUSPs structurally and functionally related to the MKPs. MKP-DUSPs, in most of the cases, are direct inactivators of MAPKs by dephosphorylation of both the Thr and the Tyr regulatory residues at the MAPKs catalytic loop. In some other cases, MKPDUSPs regulate the activity of MAPKs indirectly, acting through upstream MAPK pathways components. The active involvement of MKP-DUSPs in oncogenesis or resistance to cancer therapies is now well documented, making the search and validation of MKP-DUSPs inhibitors a prominent area in clinical cancer research. Here, we review the current knowledge on the role of MKP-DUSPs in human cancer, the status of the preclinical development and validation of specific MKP-DUSP inhibitors, and the potential of MKP-DUSPs as targets for anti-cancer drugs.
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Nunes-Xavier Caroline, Roma-Mateo Carlos, Rios Pablo, Tarrega Celine, Cejudo-Marin Rocio, Tabernero Lydia and Pulido Rafael, Dual-Specificity MAP Kinase Phosphatases as Targets of Cancer Treatment, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (1) . https://dx.doi.org/10.2174/187152011794941190
DOI https://dx.doi.org/10.2174/187152011794941190 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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