mTOR: A protein kinase switching between life and death

Pharmacological Research

Volumn 50, Issue 6, 2004, Pages 545-549

  Asnaghi, Laura ^a   Bruno, Paola ^a   Priulla, Marcella ^a   Nicolin, Angelo ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Apoptosis; Cell cycle; Microtubules; mTOR; Rapamycin

Indexed keywords

AMINO ACID; BINDING PROTEIN; EVEROLIMUS; GROWTH FACTOR; INSULIN; NOCODAZOLE; PACLITAXEL; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN S6; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE; TEMSIROLIMUS;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CELL CYCLE; CELL CYCLE G2 PHASE; CELL GROWTH; CELL PROLIFERATION; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; MAMMAL; MICROTUBULE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CELL CYCLE; CELL DEATH; HUMANS; PROTEIN KINASES;

EID: 6344256753     PISSN: 10436618     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.phrs.2004.03.007     Document Type: Review

References (43)

1. Mathews MB, Sonenberg N, Hershey JWB. Origins and principles of translational control. In: Sonenberg N, Hershey JWB, Mathews MB, editors. Translational control of gene expression. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2000. p. 1-31.
2. Schmelzle T., Hall M. TOR, a central controller of cell growth. Cell. 103:2000;253-262
3. Jacinto E., Hall M. Tor signalling in bugs, brain and brawn. Nat. Rev. Mol. Cell Biol. 4:2003;117-126
4. Sehgal S.N., Baker H., Vezina C. Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J. Antibiot. 28:1975;727-732
5. Sehgal S.N. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin. Biochem. 31:1998;335-340
6. El-Sabrout R., Delaney V., Butt F., Qadir M., Hanson P., Tuteja S., et al. Improved freedom from rejection after a loading dose of sirolimus. Transplantation. 75:2003;86-90
7. Serruys P.W., Regar E., Carter A.J. Rapamycin eluting stent: the onset of a new era in interventional cardiology. Heart. 87:2002;305-307
8. Sekulic A., Hudson C., Homme J., Yin P., Otterness D., Karnitz L., et al. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 60:2000;3504-3513
9. Huang S., Houghton P. Mechanisms of resistance to rapamycins. Drug Resist. Updates. 4:2001;378-391
10. Aoki M., Blazek E., Vogt P. A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt. Proc. Natl. Acad. Sci. USA. 98:2001;136-141
11. Podsypanina K., Lee R.T., Politis C., Hennessy I., Crane A., Puc J., et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc. Natl. Acad. Sci. USA. 98:2001;10320-10325
12. Brown E.J., Albers M.W., Shin T.B., Ichicawa K., Keith C., Lane W., et al. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature. 369:1994;756-758
13. Sabatini D.M., Erdjument-Bromage H., Lui M., Tempst P., Snyder S.H. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell. 78:1994;35-43
14. Sabers C.J., Martin M.M., Brunn G.J., Williams J., Dumont F., Wiederrecht G., et al. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J. Biol. Chem. 270:1995;815-822
15. Abraham R.T. Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling. Curr. Opin. Immunol. 10:1998;330-336
16. Helliwell S.B., Wagner P., Kunz J., Deuter-Reinhard M., Henriquez R., Hall M.N. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol. Cell Biol. 5:1994;105-118
17. Oldham S., Montagne J., Radimerski T., Thomas G., Hafen E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 14:2000;2689-2694
18. Zhang H., Stallock J.P., Ng J.C., Reinhard C., Neufeld T.P. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 14:2000;2712-2714
19. Keith C.T., Schreiber S.L. PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science. 270:1995;50-51
20. Andrade M.A., Bork P. HEAT repeats in the Huntington's disease protein. Nat. Genet. 11:1995;115-116
21. Bosotti R., Isacchi A., Sonnhammer E.L. FAT: a novel domain in PIK-related kinases. Trends Biochem. Sci. 25:2000;225-227
22. Gingras A., Raught B., Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 15:2001;807-826
23. Hardwick J.S., Kuruvilla F.G., Tong J.K., Shamji A.F., Schreiber S.L. Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. Proc. Natl. Acad. Sci. USA. 96:1999;14866-14870
24. Powers T., Walter P. Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. Mol. Biol. Cell. 10:1999;987-1000
25. Fumagalli S, Thomas G. S6 phosphorylation and signal transduction. In: Sonenberg N, Hershey JWB, Mathews MB, editors. Translational control of gene expression. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2000. p. 695-718.
26. Peterson R.T., Desai B.N., Hardwick J.S., Schreiber S.L. Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycin associated protein. Proc. Natl. Acad. Sci. USA. 96:1999;4438-4442
27. Thomas G., Hall M.N. TOR signalling and control of cell growth. Curr. Opin. Cell Biol. 9:1997;782-787
28. Hara K., Yonezawa K., Weng Q.P., Kozlowski M.T., Belham C., Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273:1998;14484-14494
29. Anthony J.C., Yoshizawa F., Anthony T.G., Vary T.C., Jefferson L.S., Kimball S.R. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J. Nutr. 130:2000;2413-2419
30. Fang Y., Vilella-Bach M., Bachmann R., Flanigan A., Chen J. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science. 294:2001;1942-1945
31. Dennis P., Jaeschke A., Saitoh M., Fowler B., Kozma S., Thomas G. Mammalian TOR: a homeostatic ATP sensor. Science. 294:2001;1102-1105
32. Vogt P.K. PI 3-kinase, mTOR, protein synthesis and cancer. Trends Mol. Med. 11:2001;482-484
33. Nave B.T., Ouwens M., Withers D.J., Alessi D.R., Shepherd P.R. Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation. Biochem. J. 344:1999;427-431
34. Yokogami K., Wakisaka S., Avruch J., Reeves S.A. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr. Biol. 10:2000;47-50
35. White R.J. Regulation of RNA polymerases I and III by the retinoblastoma protein: a mechanism for growth control? Trends Biochem. Sci. 22:1997;77-80
36. Hashemolhosseini S., Nagamine Y., Morley S.J., Desrivieres S., Mercep L., Ferrari S. Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J. Biol. Chem. 273:1998;14424-14429
37. Luo Y., Marx S.O., Kiyokawa H., Koff A., Massagué J., Marks A.R. Rapamycin resistance tied to defective regulation of p27Kip1. Mol. Cell. Biol. 16:1996;6744-6751
38. Haldar S., Basu A., Croce C.M. Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells. Cancer Res. 58:1998;1609-1615
39. Chadebech P., Brichese L., Baldin V., Vidal S., Valette A. Phosphorylation and proteasome-dependent degradation of Bcl-2 in mitotic-arrested cells after microtubule damage. Biochem. Biophys. Res. Commun. 262:1999;823-827
40. Yamamoto K., Ichijo H., Korsmeyer S.J. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol. Cell. Biol. 19:1999;8469-8478
41. Storrie B., Yang W. Dynamics of the interphase mammalian Golgi complex as revealed through drugs producing reversible Golgi disassembly. Biochim. Biophys. Acta. 14:1998;127-137
42. Calastretti A., Rancati F., Ceriani M.C., Asnaghi L., Canti G., Nicolin A. Rapamycin increases the cellular concentration of the BCL-2 protein and exerts an anti-apoptotic effect. Eur. J. Cancer. 37:2001;2121-2128
43. Calastretti A., Bevilacqua A., Ceriani C., Viganò S., Zancai P., Capaccioli S., et al. Damaged microtubules can inactivate BCL-2 by means of the mTOR kinase. Oncogene. 20:2001;6172-6180