The TOR kinases link nutrient sensing to cell growth

Rapamycin is an immunosuppressive natural product that inhibits the prolife ration of T-cells in response to nutrients and growth factors. Rapamycin bi nds to the peptidyl-prolyl isomerase FKBP12 and forms protein-drug complexe s that inhibit signal transduction by the TOR kinases. The FKBP12 and TOR p roteins are conserved from fungi to humans, and in both organisms the TOR s ignaling pathway plays a role in nutrient sensing. In response to nitrogen sources or amino acids, TOR regulates both transcription and translation, e nabling cells to appropriately respond to growth-promoting signals. Rapamyc in is having a profound impact on clinical medicine and was approved as an immunosuppressant for transplant recipients in 1999. Ongoing clinical studi es address new clinical applications for rapamycin as an antiproliferative drug for chemotherapy and invasive cardiology.