Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap.
Eukaryotic cellular mRNAs have a 5' cap structure (m7 GpppX) that facilitates binding to ribosomes and is required for efficient translation. A specific initiation factor, eIF-4F, mediates the function of the cap and consists of three subunits, one of which, eIF-4E, binds the cap. This subunit is present in limiting amounts in the cell, and is thought to be regulated by phosphorylation: decreased phosphorylation of eIF-4E following various treatments correlates with a decrease in cellular translation rate. These observations suggest that eIF-4E lies on the mitogenic signal transduction pathway, and we reasoned that overexpression of eIF-4E might profoundly affect cellular growth properties. We report here that overexpression of eIF-4E in NIH 3T3 and Rat 2 fibroblasts causes their tumorigenic transformation as determined by three criteria: formation of transformed foci on a monolayer of cells; anchorage-independent growth; and tumour formation in nude mice.
Lazaris-Karatzas
A
A
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Montine
K S
KS
Sonenberg
N
N
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003001:Cloning, Molecular; D039562:Eukaryotic Initiation Factor-4F; D015870:Gene Expression; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics; D010448:Peptide Initiation Factors / Q000502:physiology*; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction
D039562:Eukaryotic Initiation Factor-4F; D010448:Peptide Initiation Factors; D012315:RNA Caps; D012333:RNA, Messenger