Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||MAP kinase-interacting kinases - emerging targets against cancer|
|Citation:||Chemistry & Biology, 2014; 21(4):441-452|
|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; Phosphorylation|
|Rights:||© 2014 Elsevier Ltd. All rights reserved.|
|Appears in Collections:||Molecular and Biomedical Science publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.