Initiation of mRNA translation in oncogenesis: the role of eIF4E.
The eukaryotic initiation factor 4E (eIF4E) is a key regulator of protein translation whose function is activated by the Akt and Ras proto-oncogenic signal transduction pathways. eIF4E enhances the translation of mRNAs encoding several genes involved in tumorigenesis and acts as a proto-oncogene, in vitro, when overexpressed in immortalized cells. Importantly, eIF4E is frequently found overexpressed in human cancers of multiple histological origins. However, in vivo evidence of the eIF4E neoplastic potential was lacking until now. Here we discuss recent findings that demonstrate eIF4E's oncogenic role in vivo through direct genetic approaches in the mouse, and identify novel oncogenic functions for this initiation factor in cooperative tumorigenesis and response to therapy.
Montanaro
Lorenzo
L
Cancer Biology and Genetics Program, Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center,New York, New, York 10021, USA.
Pandolfi
Pier Paolo
PP
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D039561:Eukaryotic Initiation Factor-4E; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D020123:Sirolimus