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J. Biol. Chem., Vol. 276, Issue 13, 9583-9586, March 30, 2001
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,§¶
**, and§§
From the Departments of 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.
Genetics,
§ Pharmacology and Cancer Biology, ¶ Microbiology,
and Medicine, ** Howard Hughes Medical Institute, Duke University
Medical Center, Durham, North Carolina 27710
Associate investigator of the Howard Hughes Medical Institute.
§§
To whom correspondence should be addressed: Dept. of Genetics,
Box 3546, 322 CARL Bldg., Research Dr., Duke University Medical Center,
Durham, NC 27710. Tel.: 919-684-2095; Fax: 919-684-5458; E-mail:
carde004@mc.duke.edu.
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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 |
|
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 |
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 J. L. Crespo and M. N. Hall Elucidating TOR Signaling and Rapamycin Action: Lessons from Saccharomyces cerevisiae Microbiol. Mol. Biol. Rev., December 1, 2002; 66(4): 579 - 591. [Abstract] [Full Text] [PDF]
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