Epigenetic activation of a subset of mRNAs by elF4E explains its effects on cell proliferation Journal Article
| Authors: | Mamane, Y.; Petroulakis, E.; Martineau, Y.; Sato, T. A.; Larsson, O.; Rajasekhar, V. K.; Sonenberg, N. |
| Article Title: | Epigenetic activation of a subset of mRNAs by elF4E explains its effects on cell proliferation |
| Abstract: | Background. Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5′ cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E. Methodology/Principal Findings. Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Inducible expression of eIF4E resulted in increased translation of defined sets of mRNAs. Many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growth-related factors. In addition, there was augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulummediated apoptosis. Conclusions/Significance. Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a potential therapeutic option for the development of novel anti-cancer drugs. © 2007 Mamane et al. |
| Keywords: | controlled study; intercellular signaling peptides and proteins; genetics; cancer growth; nonhuman; cell proliferation; animal cell; mouse; animal; cytology; metabolism; animals; mice; cell survival; gene targeting; cell division; gene overexpression; apoptosis; small interfering rna; apoptosis regulatory proteins; physiology; endoplasmic reticulum; biosynthesis; hybrid protein; recombinant fusion proteins; messenger rna; protein synthesis; rna, messenger; microarray analysis; oligonucleotide array sequence analysis; epigenetics; 5' untranslated region; cell transformation; epigenesis, genetic; signal peptide; initiation factor 4e; rna translation; protein biosynthesis; polysome; polyribosomes; down regulation; dna microarray; genetic epigenesis; genetic code; regulatory rna sequence; cell strain 3t3; nih 3t3 cells; apoptosis regulatory protein; ribosomal proteins; ribosome protein; regulatory sequences, ribonucleic acid; 5' untranslated regions; eukaryotic initiation factor-4e; small subunit ribosomal rna |
| Journal Title: | PLoS ONE |
| Volume: | 2 |
| Issue: | 2 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2007-02-21 |
| Start Page: | e242 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0000242 |
| PUBMED: | 17311107 |
| PROVIDER: | scopus |
| PMCID: | PMC1797416 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 62" - "Export Date: 17 November 2011" - "Source: Scopus" |
