SignalSilence ® mTOR siRNA I

The mammalian target of rapamycin (mTOR, FRAP, RAFT) is a Ser/Thr protein kinase (1-3) that functions as an ATP and amino acid sensor to balance nutrient availability and cell growth (4,5). When sufficient nutrients are available, mTOR responds to a phosphatidic acid-mediated signal to transmit a positive signal to p70 S6 kinase and participate in the inactivation of the eIF4E inhibitor, 4E-BP1 (6). These events result in the translation of specific mRNA subpopulations. mTOR is phosphorylated at Ser2448 via the PI3 kinase/Akt signaling pathway and autophosphorylated at Ser2481 (7,8). mTOR plays a key role in cell growth and homeostasis and may be abnormally regulated in tumors. For these reasons, mTOR is currently under investigation as a potential target for anti-cancer therapy (9).siRNA has been used to silence mTOR expression in 293-HEK cells causing decreased raptor expression, decreased p70 S6 kinase phosphorylation, and reduced cell size (9). 1.Sabers, C.J. et al. (1995) J Biol Chem 270, 815-22. 2.Brown, E.J. et al. (1994) Nature 369, 756-8. 3.Sabatini, D.M. et al. (1994) Cell 78, 35-43. 4.Gingras, A.C. et al. (2001) Genes Dev 15, 807-26. 5.Dennis, P.B. et al. (2001) Science 294, 1102-5. 6.Fang, Y. et al. (2001) Science 294, 1942-5. 7.Navé, B.T. et al. (1999) Biochem J 344 Pt 2, 427-31. 8.Peterson, R.T. et al. (2000) J Biol Chem 275, 7416-23. 9.Huang, S. and Houghton, P.J. (2003) Curr Opin Pharmacol 3, 371-7. 10.Kim, D. H. et al. (2002) Cell 110, 163-175.