The TOR kinases link nutrient sensing to cell growth

被引:287
作者
Rohde, J
Heitman, J
Cardenas, ME
机构
[1] Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Microbiol, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
关键词
D O I
10.1074/jbc.R000034200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:9583 / 9586
页数:4
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