The relevance of mTOR protein as a target in cancer treatment

................................................................................................................3 Introduction............................................................................................................3 1 TOR /mTOR and its associated protein..........................................................................5 1.1 TOR and its associated protein in yeast........................................................................5 1.2 mTOR and its associated protein in mammalian cells.......................................................5 1.2.1 mTOR complex 1..............................................................................................5 1.2.2 mTOR complex 2..............................................................................................7 2 Major downstream targets of mTOR.............................................................................8 2.1 Phosphorylation...................................................................................................8 2.2 Brief eukaryotic translation initiation..........................................................................8 2.3 mTOR downstream targets.....................................................................................10 2.3.1 4E-BPs..........................................................................................................10 2.3.2 S6 kinase.......................................................................................................11 2.3.4 eIF4B...........................................................................................................12 2.3.5 eIF4G...........................................................................................................13 2.3.6 eEF2.............................................................................................................13 2.4 mTOR targets involved in ribosome biogenesis..............................................................................13 2.5 mTOR translational control, cell growth, and proliferation...............................................14 3 The mammalian target of rapamycin...........................................................................15 3.1 Structure of mTOR..............................................................................................15 3.2 The regulation of mTOR activity...............................................................................16 3.2.1 Control by nutrients...........................................................................................16 3.2.2 Control by growth factor....................................................................................17 3.2.2.1 PI3K/PTEN..................................................................................................17 3.2.2.2 Akt............................................................................................................18 3.2.2.3 TSC1/TSC2................................................................................................18 3.2.2.4 Rhed..........................................................................................................19 4 Cancer and mTOR.................................................................................................21 4.1 Cancer..............................................................................................................21 4.2 mTOR signaling and human cancer..........................................................................22 5 Rapamycin..........................................................................................................24 5.1 The history of rapamycin.......................................................................................24 5.2 Rapamycin and its derivatives.................................................................................24 5.3 Mechanism of action of rapamycin and its derivatives....................................................25 Conclusion............................................................................................................26