Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle

Human Molecular Genetics

Volumn 18, Issue 17, 2009, Pages 3298-3310

  Rosner, Margit ^a   Fuchs, Christiane ^a   Siegel, Nicol ^a   Valli, Alessandro ^a   Hengstschläger, Markus ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN A; CYCLIN D1; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN RAPTOR COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN RICTOR COMPLEX 2; PROTEIN KINASE B; RHEB PROTEIN; TUBERIN; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE G1 PHASE; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CELL CYCLE S PHASE; CELL MIGRATION; CELL SIZE; CONTROLLED STUDY; DOWN REGULATION; FIBROBLAST; GENE ACTIVATION; GENE FUNCTION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION;

CELL CYCLE; CELL LINE; CELL SIZE; HUMANS; MULTIPROTEIN COMPLEXES; PROTEIN KINASES;

MAMMALIA; RAPTORES;

EID: 68749116494     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddp271     Document Type: Article

References (33)

1. Wullschleger, S., Loewith, R. and Hall, M. (2006) TOR signaling in growth and metabolism. Cell, 124, 471-484.
2. Dann, S.G., Selvaraj, A. and Thomas, G. (2007) mTOR complex 1-S6K1 signaling: At the crossroads of obesity, diabetes and cancer. Trends Mol. Med., 13, 252-259.
3. Guertin, D.A. and Sabatini, D.M. (2007) Defining the role of mTOR in cancer. Cancer Cell, 12, 9-22.
4. Yang, Q. and Guan, L. (2007) Expanding mTOR signalling. Cell Res., 17, 666-681.
5. Manning, B.D. and Cantley, L.C. (2007) AKT/PKB signalling: Navigating downstream. Cell, 129, 1261-1274.
6. Rosner, M., Hanneder, M., Siegel, N., Valli, A. and Hengstschläger, M. (2008) The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting proteins. Rev. Mutat. Res., 658, 234-246.
7. Fingar, D.C., Salama, S., Tsou, C., Harlow, E. and Blenis, J. (2002) Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev., 16, 1472-1487.
8. Fingar, D.C., Richardson, C.J., Tee, A.R., Cheatham, L., Tsou, C. and Blenis, J. (2004) mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol. Cell. Biol., 24, 200-216.
9. Rosner, M., Hanneder, M., Siegel, N., Valli, A., Fuchs, C. and Hengstschläger, M. (2008) The mTOR pathway and its role in human genetic diseases. Rev. Mutat. Res., 659, 284-292.
10. Sarbassov, D.D., Ali, S.M., Sengupta, S., Sheen, J-H., Hsu, P.P., Bagley, A.F., Markhard, A.L. and Sabatini, D.M. (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell 22, 159-168.
11. Rosner, M. and Hengstschläger, M. (2008) Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: Rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. Hum. Mol. Genet., 17, 2934-2948.
12. Rosner, M., Hofer, K., Kubista, M. and Hengstschläger, M. (2003) Cell size regulation by the human TSC tumor suppression proteins depends on PI3K and FKBP38. Oncogene, 22, 4786-4798.
13. Baserga, R. (2007) Is cell size important? Cell Cycle, 6, 814-816.
14. Blagosklonny, M.V. and Pardee, A.B. (2002) The restriction point of the cell cycle. Cell Cycle, 1, 103-110.
15. Dan, H.C., Sun, M., Yang, L., Feldman, R.I., Sui, X-M., Ou, C.C., Nellist, M., Yeung, R.S., Halley, D.J.J., Nicosia, S.V., Pledger, W.J. and Cheng, J.Q. (2002) Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J. Biol. Chem., 277, 35364-35370.
16. Goncharova, E.A., Goncharov, D.A., Eszterhas, A., Hunter, D.S., Glassberg, M.K., Yeung, R.S., Walker, C.L., Noonan, D., Kwiatkowski, D.J., Chou, M.M., Panettieri, R.A. and Krymskaya, V. (2002) Tuberin regulates p70S6Kinase activation and ribosomal protein S6 phosphorylation. J. Biol. Chem., 277, 30958-30967.
17. Inoki, K., Li, Y., Zhu, T., Wu, J. and Guan, L. (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol., 4, 648-657.
18. Manning, B.D., Tee, A.R., Logsdon, M.N., Blenis, J. and Cantley, L.C. (2002) Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell., 10, 151-162.
19. Potter, C.J., Pedraza, L.G. and Xu, T. (2002) Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell. Biol., 4, 658-665.
20. Tee, A.R., Fingar, D.C., Manning, B.D., Kwiatkowski, D.J., Antley, L.C. and Blenis, J. (2002) Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signalling. Proc. Natl Acad. Sci. USA, 99, 13571-13576.
21. Fonseca, B.D., Smith, E.Q., Lee, V., MacKintosh, C. and Proud, C.G. (2007) PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signalling downstream of this complex. J. Biol. Chem., 282, 24514-24524.
22. Vander Haar, E., Lee, S-I., Bandhakavi, S., Griffin, T.J. and Kim, H. (2007) Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat. Cell. Biol., 9, 316-323.
23. Oshiro, N., Takahashi, R., Yoshino, K-C., Tanimura, K., Nakashima, A., Eguchi, S., Miyamoto, T., Hara, K., Takehana, K., Avruch, J., Kikkawa, U. and Yonezawa, K. (2007) The proline-rich Akt substrate of 40kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1. J. Biol. Chem., 282, 20329-20339.
24. Thedieck, K., Polak, P., Kim, M.L., Molle, K.D., Cohen, A., Jeno, P., Arrieumerlou, C. and Hall, M.N. (2007) PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis. PLoS ONE, 2, e1214.
25. Sancak, Y., Thoreen, C.C., Peterson, T.R., Lindquist, R.A., Kang, S.A., Spooner, E., Carr, S.A. and Sabatini, D.M. (2007) PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol. Cell. 25, 903-915.
26. Wang, L., Harris, T.E., Roth, R.A. and Lawrence, J.C. (2007) PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J. Biol. Chem., 282, 20036-20044.
27. Zhang, X., Shu, L., Hosoi, H., Murit, K.G. and Houghton, P.J. (2002) Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture. J. Biol. Chem., 277, 28127-28134.
28. Hietakangas, V. and Cohen, S.M. (2008) Tor complex 2 is needed for cell cycle progression and anchorage-independent growth of MCF7 and PC3 tumor cells. BMC Cancer, 8, 282.
29. Masri, J., Bernath, A., Martin, J., Jo, O.D., Vartanian, R., Funk, A. and Gera, J. (2007) mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor. Cancer Res. 67, 11712-11720.
30. Hietakangas, V. and Cohen, S.M. (2007) Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Genes Dev., 21, 632-637.
31. Sarbassov, D.D., Ali, S.M., Kim, D-H., Guertin, D.A., Latek, R.R., Erdjument-Bromage, H., Tempst, P. and Sabatini, D.M. (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol., 14, 1296-1302.
32. Guertin, D.A., Stevens, D.M., Thoreen, C.C., Burds, A.A., Kalaany, N.Y., Moffat, J., Brown, M., Fitzgerald, K.J. and Sabatini, D.M. (2006) Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signalling to Akt-FOXO and PKCα, but not S6K1. Dev. Cell, 11, 859-871.
33. Wang, X., Yue, P., Kim, Y.A., Fu, H., Khuri, F.R. and Sun, Y. (2008) Enhancing mammalian target of rapamycin (mTOR)-targeted cancer therapy by preventing mTOR/raptor inhibition-initiated, mTOR/rictor-independent Akt activation. Cancer Res., 68, 09-7418.