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Comment
. 2010 Aug 10;107(32):13975-6.
doi: 10.1073/pnas.1008908107. Epub 2010 Aug 2.

Mnk earmarks eIF4E for cancer therapy

Nissim Hay  1
Affiliations
Comment

Mnk earmarks eIF4E for cancer therapy

Nissim Hay. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Schematic illustration depicting the cellular pathways that lead to eIF4E activation and phosphorylation by Mnk1/2. The PI3K/Akt/mTORC1 pathway, which is frequently activated in human cancers, releases 4E-BPs from eIF4E, and enables eIF4E to bind eIF4G, which, in turn, assembles the eIF4F complex comprising eIF4E, eIF4G, eIF4A, and eIF3. Mnk1 and Mnk2, which are activated by Erk and by the stress inducible kinase p38, use eIF4G as a docking site to phosphorylate efficiently eIF4E. The phosphorylation of eIF4E is critical for its oncogenic activity, probably through the differential translation of proteins that are required for oncogenesis. The phosphorylation of eIF4E by Mnk1/2 provides a new avenue for cancer therapy. The inhibition of eIF4E phosphorylation could have similar consequences as the inhibition mTORC1 by rapalaogs, but with the advantage that it does not elicit the activation of Akt as a result of the inhibition of the negative feedback loops mediated by mTORC1.
See this image and copyright information in PMC

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