The TOR kinases link nutrient sensing to cell growth.
Rapamycin is an immunosuppressive natural product that inhibits the proliferation of T-cells in response to nutrients and growth factors. Rapamycin binds to the peptidyl-prolyl isomerase FKBP12 and forms protein-drug complexes that inhibit signal transduction by the TOR kinases. The FKBP12 and TOR proteins are conserved from fungi to humans, and in both organisms the TOR signaling pathway plays a role in nutrient sensing. In response to nitrogen sources or amino acids, TOR regulates both transcription and translation, enabling cells to appropriately respond to growth-promoting signals. Rapamycin is having a profound impact on clinical medicine and was approved as an immunosuppressant for transplant recipients in 1999. Ongoing clinical studies address new clinical applications for rapamycin as an antiproliferative drug for chemotherapy and invasive cardiology.
Departments of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
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D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008954:Models, Biological; D005810:Multigene Family; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism; D014158:Transcription, Genetic
D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D019869:Phosphatidylinositol 3-Kinases; D022061:Tacrolimus Binding Protein 1A; D020123:Sirolimus