mTOR Controls Cell Cycle Progression through Its Cell Growth Effectors S6K1 and 4E-BP1/Eukaryotic Translation Initiation Factor 4E

Molecular and Cellular Biology

Volumn 24, Issue 1, 2004, Pages 200-216

  Fingar, Diane C ^a   Richardson, Celeste J ^a   Tee, Andrew R ^a   Cheatham, Lynn ^a   Tsou, Christina ^a   Blenis, John ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOSUPPRESSIVE AGENT; INITIATION FACTOR; INITIATION FACTOR 4E; MUTANT PROTEIN; RAPAMYCIN; RNA; S6 KINASE; S6 KINASE 1; TARGET OF RAPAMYCIN KINASE; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE; CELL CYCLE G1 PHASE; CELL DIVISION; CELL GROWTH; CELL PROLIFERATION; CELL SIZE; CONTROLLED STUDY; ENZYME ACTIVITY; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; WILD TYPE;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; CELL CYCLE; CELL DIVISION; EUKARYOTIC INITIATION FACTOR-4E; MICE; PROTEIN KINASES; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; RNA INTERFERENCE; SIROLIMUS;

EUKARYOTA; MAMMALIA;

EID: 0345732640     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.24.1.200-216.2004     Document Type: Article

References (63)

1. Abraham, R. T., and G. J. Wiederrecht. 1996. Immunopharmacology of rapamycin. Annu. Rev. Immunol. 14:483-510.
2. 1 progression in yeast. Mol. Biol. Cell 7:25-42.
3. s6k integrates phosphatidylinositol 3-kinase and rapamycin-regulated signals for E2F regulation in T lymphocytes. Mol. Cell. Biol. 19:4729-4738.
4. Brown, E. J., P. A. Beal, C. T. Keith, J. Chen, T. B. Shin, and S. L. Schreiber. 1995. Control of p70 S6 kinase by kinase activity of FRAP in vivo. Nature 377:441-446.
5. Brunn, G. J., C. C. Hudson, A. Sekulic, J. M. Williams, H. Hosoi, P. J. Houghton, J. C. Lawrence, Jr., and R. T. Abraham. 1997. Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science 277:99-101.
6. Cheatham, L., M. Monfar, M. M. Chou, and J. Blenis. 1995. Structural and functional analysis of p70 S6 kinase. Proc. Natl. Acad. Sci. USA 92:11696-11700.
7. Chen, R.-H., C. Sarnecki, and J. Blenis. 1992. Nuclear localization and regulation of the erk- and rsk-encoded protein kinases. Mol. Cell. Biol. 12:915-927.
8. Choi, K. M., L. P. McMahon, and J. C. Lawrence, Jr. 2003. Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by Raptor. J. Biol. Chem. 278:19667-19673.
9. Crespo, J. L., and M. N. Hall. 2002. Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 66:579-591.
10. De Benedetti, A., S. Joshi-Barve, C. Rinker-Schaeffer, and R. E. Rhoads. 1991. Expression of antisense RNA against initiation factor eIF-4E mRNA in HeLa cells results in lengthened cell division times, diminished translation rates, and reduced levels of both eIF-4E and the p220 component of eIF-4E. Mol. Cell. Biol. 11:5435-5445.
11. Diehl, J. A., M. Cheng, M. F. Roussel, and C. J. Sherr. 1998. Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 12:3499-3511.
12. Erbay, E., and J. Chen. 2001. The mammalian target of rapamycin regulates C2C12 myogenesis via a kinase-independent mechanism. J. Biol. Chem. 276:36079-36082.
13. Fingar, D. C., S. Salama, C. Tsou, E. Harlow, and J. Blenis. 2002. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16:1472-1487.
14. Garami, A., F. J. T. Zwartkruis, T. Nobukuni, M. Joaquin, M. Roccio, H. Stocker, S. Kozma, E. Hafen, J. L. Bos, and G. Thomas. 2003. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol. Cell 11:1457-1466.
15. Gingras, A. C., B. Raught, and N. Sonenberg. 2001. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 15:807-826.
16. Hara, K., Y. Maruki, X. Long, K. Yoshino, N. Oshiro, S. Hidayat, C. Tokunaga, J. Avruch, and K. Yonezawa. 2002. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110:177-189.
17. Hara, K., K. Yonezawa, M. T. Kozlowski, T. Sugimoto, K. Andrabi, Q. P. Weng, M. Kasuga, I. Nishimoto, and J. Avruch. 1997. Regulation of eIF-4E BP1 phosphorylation by mTOR. J. Biol. Chem. 272:26457-26463.
18. Heitman, J., N. R. Mowa, and M. N. Hall. 1991. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253:905-909.
19. Jacinto, E., and M. N. Hall. 2003. Tor signalling in bugs, brain and brawn. Nat. Rev. Mol. Cell. Biol. 4:117-126.
20. Jefferies, H. B., S. Fumagalli, P. B. Dennis, C. Reinhard, R. B. Pearson, and G. Thomas. 1997. Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k. EMBO J. 16:3693-3704.
21. Jefferies, H. B. J., C. Reinhard, S. C. Kozma, and G. Thomas. 1994, Rapamycin selectively represses translation of the "polypryimidine tract" nRNA family. Proc. Natl. Acad. Sci. USA 91:4441-4445.
22. Johnston, G. C., J. R. Pringle, and L. H. Hartwell. 1977. Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. Exp. Cell Res. 105:79-98.
23. s6k defines its role in protein synthesis and rapamycin sensitivity. Proc. Natl. Acad. Sci. USA 95:5033-5038.
24. Khaleghpour, K., S. Pyronnet, A. C. Gingras, and N. Sonenberg. 1999. Translational homeostasis: eukaryotic translation initiation factor 4E control of 4E-binding protein 1 and p70 S6 kinase activities. Mol. Cell. Biol. 19:4302-4310.
25. Kim, D. H., D. D. Sarbassov, S. M. Ali, J. E. King, R. R. Latek, H. Erdjument-Bromage, P. Tempst, and D. M. Sabatini. 2002. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110:163-175.
26. 1 progression. Nature 363:170-172.
27. Lazaris-Karatzas, A., K. S. Montine, and N. Sonenberg. 1990. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap. Nature 345:544-547.
28. Loewith, R., E. Jacinto, S. Wullschleger, A. Lorberg, J. L. Crespo, D. Bonenfant, W. Oppliger, P. Jenoe, and M. N. Hall. 2002. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10:457-468.
29. Martin, K. A., and J. Blenis. 2002. Coordinate regulation of translation by the PI 3-kinase and mTOR pathways. Adv. Cancer Res. 86:1-39.
30. Martin, K. A., S. S. Schalm, C. Richardson, A. Romanelli, K. L. Keon, and J. Blenis. 2001. Regulation of ribosomal S6 kinase 2 by effectors of the phosphoinositide 3-kinase pathway. J. Biol. Chem. 276:7884-7891.
31. McManus, E. J., and D. R. Alessi. 2002. TSC1-TSC2: a complex tale of PKB-mediated S6K regulation. Nat. Cell Biol. 4:E214-E216.
32. Neufeld, T. P., A. F. de la Cruz, L. A. Johnston, and B. A. Edgar. 1998. Coordination of growth and cell division in the Drosophila wing. Cell 93:1183-1193.
33. Nojima, H., C. Tokunaga, S. Eguchi, N. Oshiro, S. Hidayat, K. Yoshino, K. Hara, N. Tanaka, J. Avruch, and K. Yonezawa. 2003. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J. Biol. Chem. 278:15461-15464.
34. Oldham, S., and E. Hafen. 2003. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 13:79-85.
35. Oldham, S., J. Montagne, T. Radimerski, G. Thomas, and E. Hafen. 2000. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 14:2689-2694.
36. 1 events and regulation of cell proliferation. Science 246:603-608.
37. s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain. EMBO J. 14:5279-5287.
38. 1 cyclin CLN3 in yeast. Genes Dev. 11:2522-2531.
39. Rohde, J., J. Heitman, and M. E. Cardenas. 2001. The TOR kinases link nutrient sensing to cell growth. J. Biol. Chem. 276:9583-9586.
40. cip1 regulates PCNA binding and proliferation of endothelial cells. Mol. Cell. Biol. 21:5644-5657.
41. Rousseau, D., A. C. Gingras, A. Pause, and N. Sonenberg. 1996. The eIF4E-binding proteins 1 and 2 are negative regulators of cell growth. Oncogene 13:2415-2420.
42. Rousseau, D., R. Kaspar, I. Rosenwald, L. Gehrke, and N. Sonenberg. 1996. Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc. Natl. Acad. Sci. USA 93:1065-1070.
43. Saucedo, L. J., X. Gao, D. A. Chiarelli, L. Li, D. Pan, and B. A. Edgar. 2003. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol. 5:566-571.
44. Schalm, S. S., and J. Blenis. 2002. Identification of a conserved motif required for mTOR signaling. Curr. Biol. 12:632-639.
45. Schalm, S. S., D. C. Fingar, D. M. Sabatini, and J. Blenis. 2003. TOS motif-mediated Raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr. Biol. 13:797-806.
46. Schmelzle, T., and M. N. Hall. 2000. TOR, a central controller of cell growth. Cell 103:253-262.
47. s6k gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J. 17:6649-6659.
48. Sonenberg, N., and A. C. Gingras. 1998. The mRNA 5′ cap-binding protein eIF4E and control of cell growth. Curr. Opin. Cell Biol. 10:268-275.
49. Stocker, H., T. Radimerski, B. Schindelholz, F. Wittwer, P. Belawat, P. Daram, S. Breuer, G. Thomas, and E. Hafen. 2003. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat. Cell Biol. 5:559-566.
50. Stolovich, M., H. Tang, E. Hornstein, G. Levy, R. Cohen, S. S. Bae, M. J. Birnbaum, and O. Meyuhas. 2002. Transduction of growth or mitogenic signals into translational activation of TOP mRNAs is fully reliant on the phosphatidylinositol 3-kinase-mediated pathway but requires neither S6K1 nor rpS6 phosphorylation. Mol. Cell. Biol. 22:8101-8113.
51. Strudwick, S., and K. L. Borden. 2002. The emerging roles of translation factor eIF4E in the nucleus. Differentiation 70:10-22.
52. Sui, G., C. Soohoo, B. Affar el, F. Gay, Y. Shi, and W. C. Forrester. 2002. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc. Natl. Acad. Sci. USA 99:5515-5520.
53. Tang, H., E. Hornstein, M. Stolovich, G. Levy, M. Livingstone, D. Templeton, J. Avruch, and O. Meyuhas. 2001. Amino acid-induced translation of TOP mRNAs is fully dependent on phosphatidylinositol 3-kinase-mediated signaling, is partially inhibited by rapamycin, and is independent of S6K1 and rpS6 phosphorylation. Mol. Cell. Biol. 21:8671-8683.
54. Tee, A. R., B. D. Manning, P. P. Roux, L. C. Cantley, and J. Blenis. 2003. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr. Biol. 13:1259-1268.
55. Tee, A. R., and C. G. Proud. 2002. Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motif. Mol. Cell. Biol. 22:1674-1683.
56. Terada, N., H. R. Patel, K. Takase, K. Kohno, A. C. Nairn, and E. W. Gelfand. 1994. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc. Natl. Acad. Sci. USA 91:11477-11481.
57. 1 progression. J. Biol. Chem. 274:4266-4272.
58. Vinals, F., J. C. Chambard, and J. Pouyssegur. 1999. p70 S6 kinase-mediated protein synthesis is a critical step for vascular endothelial cell proliferation. J. Biol. Chem. 274:26776-26782.
59. Wang, X., W. Li, J. L. Parra, A. Beugnet, and C. G. Proud. 2003. The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation. Mol. Cell. Biol. 23:1546-1557.
60. Wilson, K. F., W. J. Wu, and R. A. Cerione. 2000. Cdc42 stimulates RNA splicing via the S6 kinase and a novel S6 kinase target, the nuclear cap-binding complex. J. Biol. Chem. 275:37307-37310.
61. Zhang, H., J. P. Stallock, J. C. Ng, C. Reinhard, and T. P. Neufeld. 2000. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 14:2712-2724.
62. Zhang, Y., X. Gao, L. J. Saucedo, B. Ru, B. A. Edgar, and D. Pan. 2003. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 5:578-581.
63. WAFI by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat. Cell Biol. 3:245-252.