Epigenetic activation of a subset of mRNAs by eIF4E explains its effects on cell proliferation.
PLoS One, 2007/2/21;2(2):e242.
Mamane Y[1], Petroulakis E, Martineau Y, Sato TA, Larsson O, Rajasekhar VK, Sonenberg N
Affiliations
PMID: 17311107
Impact factor: 3.752
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 reticulum-mediated 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.
MeSH terms
5' Untranslated Regions; Animals; Apoptosis; Apoptosis Regulatory Proteins; Cell Division; Epigenesis, Genetic; Eukaryotic Initiation Factor-4E; Intercellular Signaling Peptides and Proteins; Mice; NIH 3T3 Cells; Oligonucleotide Array Sequence Analysis; Polyribosomes; Protein Biosynthesis; RNA, Messenger; Recombinant Fusion Proteins; Regulatory Sequences, Ribonucleic Acid; Ribosomal Proteins
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