Epigenetic activation of a subset of mRNAs by eIF4E explains its effects on cell proliferation.
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.


RESULTS
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
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.
Mamane
Yaël
Y
Department of Biochemistry, McGill Cancer Centre, McGill University, Montreal, Quebec, Canada.
Petroulakis
Emmanuel
E
Martineau
Yvan
Y
Sato
Taka-Aki
TA
Larsson
Ola
O
Rajasekhar
Vinagolu K
VK
Sonenberg
Nahum
N
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D044127:Epigenesis, Genetic; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics
D020121:5' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D039561:Eukaryotic Initiation Factor-4E; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D012269:Ribosomal Proteins