Dissecting eIF4E action in tumorigenesis

Wendel, H. G., Silva, R. L., Malina, A., Mills, J. R., Zhu, H., Ueda, T., Watanabe-Fukunaga, R., Fukunaga, R., Teruya-Feldstein, J., Pelletier, J., Lowe, S. W. (December 2007) Dissecting eIF4E action in tumorigenesis. Genes Dev, 21 (24). pp. 3232-7.

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URL: https://www.ncbi.nlm.nih.gov/pubmed/18055695
DOI: 10.1101/gad.1604407

Abstract

Genetically engineered mouse models are powerful tools for studying cancer genes and validating targets for cancer therapy. We previously used a mouse lymphoma model to demonstrate that the translation initiation factor eIF4E is a potent oncogene in vivo. Using the same model, we now show that the oncogenic activity of eIF4E correlates with its ability to activate translation and become phosphorylated on Ser 209. Furthermore, constitutively activated MNK1, an eIF4E Ser 209 kinase, promotes tumorigenesis in a manner similar to eIF4E, and a dominant-negative MNK mutant inhibits the in vivo proliferation of tumor cells driven by mutations that deregulate translation. Phosphorylated eIF4E promotes tumorigenesis primarily by suppressing apoptosis and, accordingly, the anti-apoptotic protein Mcl-1 is one target of both phospho-eIF4E and MNK1 that contributes to tumor formation. Our results provide insight into how eIF4E contributes to tumorigenesis and pinpoint a level of translational control that may be suitable for therapeutic intervention.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders > cancer > cancer types > lymphoma
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: 15 December 2007
Date Deposited: 31 Aug 2011 00:01
Last Modified: 10 Apr 2018 20:43
PMCID: PMC2113024
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15275

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