A Chemical Genetic Screen for mTOR Pathway Inhibitors Based on 4E-BP-Dependent Nuclear Accumulation of eIF4E

Chemistry and Biology

Volumn 16, Issue 12, 2009, Pages 1240-1249

  Livingstone, Mark ^a   Larsson, Ola ^a   Sukarieh, Rami ^a   Pelletier, Jerry ^a   Sonenberg, Nahum ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

CELLBIO; CHEMBIO; SIGNALING

Indexed keywords

MAMMALIA;

EID: 73149094720     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2009.11.010     Document Type: Article

References (63)

1. Abraham R.T., and Eng C.H. Mammalian target of rapamycin as a therapeutic target in oncology. Expert Opin. Ther. Targets 12 (2008) 209-222
2. Bain J., Plater L., Elliott M., Shpiro N., Hastie C.J., McLauchlan H., Klevernic I., Arthur J.S., Alessi D.R., and Cohen P. The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408 (2007) 297-315
3. Ballou L.M., Selinger E.S., Choi J.Y., Drueckhammer D.G., and Lin R.Z. Inhibition of mammalian target of rapamycin signaling by 2-(morpholin-1-yl)pyrimido[2,1-alpha]isoquinolin-4-one. J. Biol. Chem. 282 (2007) 24463-24470 Epub 22007, 24411
4. Choo A.Y., and Blenis J. TORgeting oncogene addiction for cancer therapy. Cancer Cell 9 (2006) 77-79
5. Dasgupta B., Yi Y., Chen D.Y., Weber J.D., and Gutmann D.H. Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Cancer Res. 65 (2005) 2755-2760
6. Dasgupta B., Yi Y., Hegedus B., Weber J.D., and Gutmann D.H. Cerebrospinal fluid proteomic analysis reveals dysregulation of methionine aminopeptidase-2 expression in human and mouse neurofibromatosis 1-associated glioma. Cancer Res. 65 (2005) 9843-9850
7. Dostie J., Ferraiuolo M., Pause A., Adam S.A., and Sonenberg N. A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5′ cap-binding protein, eIF4E. EMBO J. 19 (2000) 3142-3156
8. Edinger A.L., Linardic C.M., Chiang G.G., Thompson C.B., and Abraham R.T. Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Res. 63 (2003) 8451-8460
9. Engelman J.A., Chen L., Tan X., Crosby K., Guimaraes A.R., Upadhyay R., Maira M., McNamara K., Perera S.A., Song Y., et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med. 14 (2008) 1351-1356
10. Fan Q.W., Knight Z.A., Goldenberg D.D., Yu W., Mostov K.E., Stokoe D., Shokat K.M., and Weiss W.A. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell 9 (2006) 341-349
11. Fan Q.W., Cheng C.K., Nicolaides T.P., Hackett C.S., Knight Z.A., Shokat K.M., and Weiss W.A. A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma. Cancer Res. 67 (2007) 7960-7965
12. Feldman M.E., Apsel B., Uotila A., Loewith R., Knight Z.A., Ruggero D., and Shokat K.M. Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2. PLoS Biol. 7 (2009) e38
13. Furic L., Livingstone M., Dowling R.J., and Sonenberg N. Targeting mtor-dependent tumours with specific inhibitors: a model for personalized medicine based on molecular diagnoses. Curr. Oncol. 16 (2009) 59-61
14. Garcia-Martinez J.M., and Alessi D.R. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem. J. 416 (2008) 375-385
15. Gingras A.C., Kennedy S.G., O'Leary M.A., Sonenberg N., and Hay N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 12 (1998) 502-513
16. Griffith E.C., Su Z., Turk B.E., Chen S., Chang Y.H., Wu Z., Biemann K., and Liu J.O. Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin. Chem. Biol. 4 (1997) 461-471
17. Guan L., Song K., Pysz M.A., Curry K.J., Hizli A.A., Danielpour D., Black A.R., and Black J.D. Protein kinase C-mediated down-regulation of cyclin D1 involves activation of the translational repressor 4E-BP1 via a phosphoinositide 3-kinase/Akt-independent, protein phosphatase 2A-dependent mechanism in intestinal epithelial cells. J. Biol. Chem. 282 (2007) 14213-14225 Epub 12007, 14213
18. Guertin D.A., Stevens D.M., Saitoh M., Kinkel S., Crosby K., Sheen J.H., Mullholland D.J., Magnuson M.A., Wu H., and Sabatini D.M. mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell 15 (2009) 148-159
19. Haghighat A., Mader S., Pause A., and Sonenberg N. Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 14 (1995) 5701-5709
20. Haney S.A. High Content Screening: Science, Techniques, and Applications (2008), Wiley-Interscience, Hoboken, N.J.
21. Hara K., Maruki Y., Long X., Yoshino K., Oshiro N., Hidayat S., Tokunaga C., Avruch J., and Yonezawa K. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110 (2002) 177-189
22. Hizli A.A., Black A.R., Pysz M.A., and Black J.D. Protein kinase C alpha signaling inhibits cyclin D1 translation in intestinal epithelial cells. J. Biol. Chem. 281 (2006) 14596-14603 Epub 12006, 14523
23. Hresko R.C., and Mueckler M. mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. J. Biol. Chem. 280 (2005) 40406-40416
24. Ikenoue T., Inoki K., Yang Q., Zhou X., and Guan K.L. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 27 (2008) 1919-1931 Epub 2008 Jun 1919
25. Jacinto E., Loewith R., Schmidt A., Lin S., Ruegg M.A., Hall A., and Hall M.N. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat. Cell Biol. 6 (2004) 1122-1128
26. Kau T.R., Schroeder F., Ramaswamy S., Wojciechowski C.L., Zhao J.J., Roberts T.M., Clardy J., Sellers W.R., and Silver P.A. A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells. Cancer Cell 4 (2003) 463-476
27. Kedersha N., Stoecklin G., Ayodele M., Yacono P., Lykke-Andersen J., Fritzler M.J., Scheuner D., Kaufman R.J., Golan D.E., and Anderson P. Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J. Cell Biol. 169 (2005) 871-884
28. Kim J.E., and Chen J. Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation. Proc. Natl. Acad. Sci. USA 97 (2000) 14340-14345
29. Kim D.H., Sarbassov D.D., Ali S.M., King J.E., Latek R.R., Erdjument-Bromage H., Tempst P., and Sabatini D.M. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110 (2002) 163-175
30. Kimball S.R., and Horetsky R.L. Alterations in interprotein interactions between translation initiation factors assessed by fluorescence resonance energy transfer. Int. J. Biochem. Cell Biol. 33 (2001) 797-806
31. Kleijn M., Scheper G.C., Wilson M.L., Tee A.R., and Proud C.G. Localisation and regulation of the eIF4E-binding protein 4E-BP3. FEBS Lett. 532 (2002) 319-323
32. Knight Z.A., Gonzalez B., Feldman M.E., Zunder E.R., Goldenberg D.D., Williams O., Loewith R., Stokoe D., Balla A., Toth B., et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell 125 (2006) 733-747
33. Konaklieva M.I., and Plotkin B.J. Lactones: generic inhibitors of enzymes?. Mini Rev. Med. Chem. 5 (2005) 73-95
34. Kowluru A., Seavey S.E., Rabaglia M.E., Nesher R., and Metz S.A. Carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting cells: evidence for functional consequences on enzyme activity and insulin secretion. Endocrinology 137 (1996) 2315-2323
35. Lang V., Zanchin N.I., Lunsdorf H., Tuite M., and McCarthy J.E. Initiation factor eIF-4E of Saccharomyces cerevisiae. Distribution within the cell, binding to mRNA, and consequences of its overproduction. J. Biol. Chem. 269 (1994) 6117-6123
36. Lejbkowicz F., Goyer C., Darveau A., Neron S., Lemieux R., and Sonenberg N. A fraction of the mRNA 5′ cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus. Proc. Natl. Acad. Sci. USA 89 (1992) 9612-9616
37. Livingstone M., Ruan H., Weiner J., Clauser K.R., Strack P., Jin S., Williams A., Greulich H., Gardner J., Venere M., et al. Valosin-containing protein phosphorylation at Ser784 in response to DNA damage. Cancer Res. 65 (2005) 7533-7540
38. Loewith R., Jacinto E., Wullschleger S., Lorberg A., Crespo J.L., Bonenfant D., Oppliger W., Jenoe P., and Hall M.N. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10 (2002) 457-468
39. Maira S.M., Stauffer F., Brueggen J., Furet P., Schnell C., Fritsch C., Brachmann S., Chene P., De Pover A., Schoemaker K., et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol. Cancer Ther. 7 (2008) 1851-1863
40. Mora A., Komander D., van Aalten D.M., and Alessi D.R. PDK1, the master regulator of AGC kinase signal transduction. Semin. Cell Dev. Biol. 15 (2004) 161-170
41. Oh N., Kim K.M., Cho H., Choe J., and Kim Y.K. Pioneer round of translation occurs during serum starvation. Biochem. Biophys. Res. Commun. 362 (2007) 145-151 Epub 2007 Aug 2008
42. Oshiro N., Yoshino K., Hidayat S., Tokunaga C., Hara K., Eguchi S., Avruch J., and Yonezawa K. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells 9 (2004) 359-366
43. Pause A., Belsham G.J., Gingras A.C., Donze O., Lin T.A., Lawrence Jr. J.C., and Sonenberg N. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5′-cap function. Nature 371 (1994) 762
44. Peterson R.T., and Schreiber S.L. Kinase phosphorylation: Keeping it all in the family. Curr. Biol. 9 (1999) R521-R524
45. Rong L., Livingstone M., Sukarieh R., Petroulakis E., Gingras A.C., Crosby K., Smith B., Polakiewicz R.D., Pelletier J., Ferraiuolo M.A., et al. Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs. RNA 14 (2008) 1318-1327
46. Rosen N., and She Q.B. AKT and cancer-is it all mTOR?. Cancer Cell 10 (2006) 254-256
47. Roux P.P., Ballif B.A., Anjum R., Gygi S.P., and Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc. Natl. Acad. Sci. USA 101 (2004) 13489-13494
48. Sabatini D.M. mTOR and cancer: insights into a complex relationship. Nat. Rev. Cancer 6 (2006) 729-734 Epub 2006 Aug 2017
49. Sarbassov D.D., Ali S.M., Kim D.H., Guertin D.A., Latek R.R., Erdjument-Bromage H., Tempst P., and Sabatini D.M. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 14 (2004) 1296-1302
50. Sarbassov D.D., Guertin D.A., Ali S.M., and Sabatini D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307 (2005) 1098-1101
51. Smith I.J., and Dodd S.L. Calpain activation causes a proteasome-dependent increase in protein degradation and inhibits the Akt signalling pathway in rat diaphragm muscle. Exp. Physiol. 92 (2007) 561-573
52. Tan E.W., and Rando R.R. Identification of an isoprenylated cysteine methyl ester hydrolase activity in bovine rod outer segment membranes. Biochemistry 31 (1992) 5572-5578
53. Thoreen C.C., Kang S.A., Chang J.W., Liu Q., Zhang J., Gao Y., Reichling L.J., Sim T., Sabatini D.M., and Gray N.S. An ATP-competitive mTOR inhibitor reveals rapamycin-insensitive functions of mTORC1. J. Biol. Chem. 284 (2009) 8023-8032
54. Toschi A., Lee E., Xu L., Garcia A., Gadir N., and Foster D.A. Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: a competition with rapamycin. Mol. Cell. Biol. 29 (2009) 1411-1420
55. Vlahos C.J., Matter W.F., Hui K.Y., and Brown R.F. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 269 (1994) 5241-5248
56. Walker E.H., Pacold M.E., Perisic O., Stephens L., Hawkins P.T., Wymann M.P., and Williams R.L. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell 6 (2000) 909-919
57. Wan X., Harkavy B., Shen N., Grohar P., and Helman L.J. Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene 26 (2007) 1932-1940
58. Wang E., Norred W.P., Bacon C.W., Riley R.T., and Merrill Jr. A.H. Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. J. Biol. Chem. 266 (1991) 14486-14490
59. Weinstein I.B. Cancer. Addiction to oncogenes-the Achilles heal of cancer. Science 297 (2002) 63-64
60. Xu G.F., O'Connell P., Viskochil D., Cawthon R., Robertson M., Culver M., Dunn D., Stevens J., Gesteland R., White R., et al. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62 (1990) 599-608
61. Yang J., Shamji A., Matchacheep S., and Schreiber S.L. Identification of a small-molecule inhibitor of class Ia PI3Ks with cell-based screening. Chem. Biol. 14 (2007) 371-377
62. Yu K., Toral-Barza L., Shi C., Zhang W.G., Lucas J., Shor B., Kim J., Verheijen J., Curran K., Malwitz D.J., et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res. 69 (2009) 6232-6240
63. Zhang X., Shu L., Hosoi H., Murti K.G., and Houghton P.J. Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture. J. Biol. Chem. 277 (2002) 28127-28134