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Papers In Press, published online ahead of print February 2, 2001
Department of Genetics, Duke University Medical Center, Durham, NC 27710
Corresponding Author: carde004{at}mc.duke.edu
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 antiproliferative drugs for chemotherapy and invasive cardiology.
J. Biol. Chem, 10.1074/jbc.R000034200
Submitted on December 27, 2000
Revised on January 30, 2001
Accepted on February 2, 2001
The TOR kinases link nutrient sensing to cell growth
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