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Type: Journal article
Title: MAP kinase-interacting kinases - emerging targets against cancer
Author: Diab, S.
Kumarasiri, M.
Yu, M.
Teo, T.
Proud, C.
Milne, R.
Wang, S.
Citation: Chemistry and Biology, 2014; 21(4):441-452
Publisher: Cell Press
Issue Date: 2014
ISSN: 1074-5521
Statement of
Sarah Diab, Malika Kumarasiri, Mingfeng Yu, Theodosia Teo, Christopher Proud, Robert Milne, Shudong Wang
Abstract: Mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) regulate the initiation of translation through phosphorylation of eukaryotic initiation factor 4E (eIF4E). Mnk-mediated eIF4E activation promotes cancer development and progression. While the phosphorylation of eIF4E is necessary for oncogenic transformation, the kinase activity of Mnks seems dispensable for normal development. For this reason, pharmacological inhibition of Mnks could represent an ideal mechanism-based and nontoxic therapeutic strategy for cancer treatment. In this review, we discuss the current understanding of Mnk biological roles, structures, and functions, as well as clinical implications. Importantly, we propose different strategies for identification of highly selective small molecule inhibitors of Mnks, including exploring a structural feature of their kinase domain, DFD motif, which is unique within the human kinome. We also argue that a combined targeting of Mnks and other pathways should be considered given the complexity of cancer.
Keywords: Protein-Serine-Threonine Kinases
Eukaryotic Initiation Factor-4E
Antineoplastic Agents
Protein Kinase Inhibitors
Structure-Activity Relationship
Rights: © 2014 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.chembiol.2014.01.011
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Appears in Collections:Aurora harvest 3
Molecular and Biomedical Science publications

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