Dissecting eIF4E action in tumorigenesis Journal Article


Authors: Wendel, H. G.; Silva, R. L. A.; Malina, A.; Mills, J. R.; Zhu, H.; Ueda, T.; Watanabe-Fukunaga, R.; Fukunaga, R.; Teruya-Feldstein, J.; Pelletier, J.; Lowe, S. W.
Article Title: Dissecting eIF4E action in tumorigenesis
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. © 2007 by Cold Spring Harbor Laboratory Press.
Keywords: controlled study; protein phosphorylation; unclassified drug; gene mutation; nonhuman; flow cytometry; cell proliferation; animal cell; mouse; animals; mice; gene; cells, cultured; apoptosis; signaling; serine; neoplasm proteins; analytic method; animal experiment; protein; phosphorylation; carcinogenesis; mice, transgenic; tumorigenesis; cell transformation, neoplastic; blotting, western; correlation analysis; protein-serine-threonine kinases; protein mcl 1; rna translation; translation; base sequence; dna primers; proto-oncogene proteins c-bcl-2; eukaryotic initiation factor-4e; enzyme; mouse model; eif4e protein; mnk 1 enzyme; protein serine kinase; eif4e gene
Journal Title: Genes and Development
Volume: 21
Issue: 24
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2007-12-15
Start Page: 3232
End Page: 3237
Language: English
DOI: 10.1101/gad.1604407
PUBMED: 18055695
PROVIDER: scopus
PMCID: PMC2113024
DOI/URL:
Notes: --- - "Cited By (since 1996): 94" - "Export Date: 17 November 2011" - "CODEN: GEDEE" - "Source: Scopus"
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MSK Authors
  1. Julie T Feldstein
    293 Feldstein
  2. Ricardo Luis Alves Silva
    3 Silva
  3. Hans Guido Wendel
    80 Wendel
  4. Hong Zhu
    2 Zhu