Retroviral oncogenes and TOR.
Retroviruses have recruited the catalytic subunit of PI 3-kinase and its downstream target, Akt, as oncogenes. These viruses cause tumors in animals and induce oncogenic transformation in cell culture. The oncogenicity of these viruses is specifically inhibited by rapamycin; retroviruses carrying other oncogenes are insensitive to this macrolide antibiotic. Rapamycin is an inhibitor of the TOR (target of rapamycin) kinase whose downstream targets include p70 S6 kinase and the negative regulator of translation initiation 4E-BP. Emerging evidence suggests that the TOR signals transmitted to the translational machinery are essential for oncogenic transformation by the PI 3-kinase pathway.
Aoki
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Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC-239, La Jolla, CA 92037, USA.
Vogt
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PK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D002472:Cell Transformation, Viral / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009857:Oncogenes / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C494918:AKT1 protein, human