The zinc finger protein GLI induces cellular sensitivity to the mTOR inhibitor rapamycin

Cell Growth and Differentiation

Volumn 10, Issue 7, 1999, Pages 503-516

  Louro, Iuri D ^a   McKie Bell, Peggy ^c   Gosnell, Helen ^a   Brindley, Bianca C ^d   Bucy, R Patrick ^b   Ruppert, J Michael ^a,c,e  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b University of Alabama at Birmingham   (United States)

^c University of Alabama at Birmingham   (United States)

^d UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

^e University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BROXURIDINE; PROTEIN GLI; RAPAMYCIN; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN;

ANIMAL CELL; ARTICLE; CELL CYCLE; CELL PROLIFERATION; DRUG SENSITIVITY; GENE EXPRESSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN METABOLISM; PROTEIN SYNTHESIS; PROTEIN SYNTHESIS INHIBITION; RAT;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; CELL CYCLE; CELL TRANSFORMATION, NEOPLASTIC; CELLS, CULTURED; CLONE CELLS; GENES, MYC; GENES, RAS; IMMUNOSUPPRESSIVE AGENTS; MICE; MICE, NUDE; NEOPLASM TRANSPLANTATION; ONCOGENE PROTEINS; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); PROTEIN BIOSYNTHESIS; PROTEIN KINASES; RHABDOMYOSARCOMA, ALVEOLAR; RHABDOMYOSARCOMA, EMBRYONAL; SIROLIMUS; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS; TRANSFECTION; TRANSPLANTATION, HETEROLOGOUS; ZINC FINGERS;

ANIMALIA; ERINACEIDAE;

EID: 0032764126     PISSN: 10449523     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (95)

1. Kinzler, K. W., Bigner, S. H., Bigner, D. D., Trent, J. M., Law, M. L., O'Brien, S. J., Wong, A. J., and Vogelstein, B. Identification of an amplified, highly expressed gene in a human glioma. Science (Washington DC), 236: 70-73, 1987.
2. Kinzler, K. W., Ruppert, J. M., Bigner, S. H., and Vogelstein, B. The GLI gene is a member of the Krüppel family of zinc finger proteins. Nature (Lond.), 332: 371-374, 1988.
3. Roberts, W. M., Douglass, E. C., Peiper, S. C., Houghton, P. J., and Look, A. T. Amplification of the GLI gene in childhood sarcomas. Cancer Res., 49: 5407-5413, 1989.
4. Salgaller, M., Pearl, D., and Stephens, R. In situ hybridization with single-stranded RNA probes to demonstrate infrequently elevated GLI mRNA and no increased RAS mRNA levels in meningiomas and astrocytomas. Cancer Lett., 57: 243-253, 1991.
5. Khatib, Z. A., Matsushime, H., Valentine, M., Shapiro, D. N., Sherr, C. J., and Look, A. T. Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res., 53: 5535-5541, 1993.
6. Ruppert, J. M., Kinzler, K. W., Wong, A. J., Bigner, S. H., Kao, F-T., Law, M. L., Seuanez, H. N., O'Brien, S. J., and Vogelstein, B. The GLI-Kruppel family of human genes. Mol. Cell. Biol., 8: 3104-3113, 1988.
7. Ruppert, J. M., Vogelstein, B., Arheden, K., and Kinzler, K. W. GLI3 encodes a 190kd protein with multiple regions of GLI similarity. Mol. Cell. Biol., 10: 5408-5415, 1990.
8. Hui, C. C., Slusarski, D., Platt, K. A., Holmgren, R., and Joyner, A. L. Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, gli, gli-2, and gli-3, in ectoderm- and mesoderm-derived tissues suggests multiple roles during postimplantation develop-ment. Dev. Biol., 162: 402-413, 1994.
9. Vandenheuvel, M., and Lngham, P. W. Smoothening the path for hedgehogs. Trends Cell Biol., 6: 451-453, 1996.
10. Dominguez, M., Brunner, M., Hafen, E., and Basler, K. Sending and receiving the hedgehog signal: control by the Drosophila gli protein cubitus interruptus. Science (Washington DC), 272: 1621-1625, 1996.
11. Maroto, M., Reshef, R., Munsterberg, A. E., Koester, S., Goulding, M., and Lassar, A. B. Ectopic pax-3 activates myo-d and myf-5 expression in embryonic mesoderm and neural tissue. Cell, 89: 139-148, 1997.
12. Lee, J., Platt, K. A., Censullo, P., and Ruiz i Altaba, A. Gli1 is a target of sonic hedgehog that induces ventral neural tube development. Development (Camb.), 124: 2537-2552, 1997.
13. Grindley, J. C., Bellusci, S., Perkins, D., and Hogan, B. L. M. Evidence for the involvement of the gli gene family in embryonic mouse lung development. Dev. Biol., 188: 337-348, 1997.
14. Scott, M. P. Hox genes, arms and the man. Nat. Genet., 15: 117-118, 1997.
15. Alcedo, J., Ayzenzon, M., Von Ohlen, T., Noll, M., and Hooper, J. E. The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell, 86: 221-232, 1996.
16. Alexandre, C., Jacinto, A., and Lngham, P. W. Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Genes Dev., 10: 2003-2013, 1996.
17. Stone, D. M., Hynes, M., Armanini, M., Swanson, T. A., Gu, Q., Johnson, R. L., Scott, M. P., Pennica, D., Goddard, A., Phillips, H., Noll, M., Hooper, J. E., de Sauvage, F., and Rosenthal, A. The tumour-suppressor gene patched encodes a candidate receptor for sonic hedgehog. Nature (Lond.), 384: 129-134, 1996.
18. van den Heuvel, M., and Ingham, P. W. smoothened encodes a receptor-like serpentine protein required for hedgehog signaling. Nature (Lond.), 382: 547-551, 1996.
19. Vonohlen, T., Lessing, D., Nusse, R., and Hooper, J. E. Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein. Proc. Natl. Acad. Sci. USA, 94: 2404-2409, 1997.
20. Edgar, B. A., and Lehner, C. F. Developmental control of cell cycle regulators-a fly's perspective. Science (Washington DC), 274: 1646-1652, 1996.
21. Johnson, R. L., Grenier, J. K., and Scott, M. P. patched overexpression alters wing disc size and pattern: transcriptional and post-transcriptional effects on hedgehog targets. Development (Camb.), 121: 4161-4170, 1995.
22. Goodrich, L. V., Johnson, R. L., Milenkovic, L, McMahon, J. A., and Scott, M. P. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by hedgehog. Genes Dev., 10: 301-312, 1996.
23. Ingham, P. W. The patched gene in development and cancer. Curr. Opin. Genet. Dev., 8: 88-94, 1998.
24. Ohlmeyer, J. T., and Kalderon, D. Hedgehog stimulates maturation of cubitus interruptus into a labile transcriptional activator. Nature (Lond.), 396: 749-753, 1998.
25. Shin, S. H., Kogerman, P., Lindstrom, E., Toftgard, R., and Biesecker, L. G. Gli3 mutations in human disorders mimic Drosophila cubitus interruptus protein functions and localization. Proc. Natl. Acad. Sci. USA, 96: 2880-2884, 1999.
26. Dai, P., Akimaru, H., Tanaka, Y., Maekawa, T., Nakafuku, M., and Ishii, S. Sonic hedgehog-induced activation of the GLI-1 promoter is mediated by GLI-3. J. Biol. Chem., 274: 8143-8152, 1999.
27. Dahmane, N., Lee, J., Robins, P., Heller, P., and Ruiz i Altaba, A. Activation of the transcription factor GLI-1 and the sonic hedgehog signalling pathway in skin tumours. Nature (Lond.), 389: 876-881, 1997.
28. Xie, J. W., Murone, M., Luoh, S. M., Ryan, A., Gu, Q. M., Zhang, C. H., Bonifas, J. M., Lam, C. W., Hynes, M., Goddard, A., Rosenthal, A., Epstein, E. H., and de Sauvage, F. J. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature (Lond.), 391: 90-92, 1998.
29. Green, J., Leigh, I. M., Poulsom, R., and Quinn, A. G. Basal cell carcinoma development is associated with induction of the expression of the transcription factor GLI-1. Br. J. Dermatol., 139: 911-915, 1998.
30. Bale, A. E. The nevoid basal cell carcinoma syndrome: genetics and mechanism of carcinogenesis. Cancer Investig., 15: 180-186, 1997.
31. Hahn, H., Wicking, C., Zaphiropoulous, P. G., Gailani, M. R., Shanley, S., Chidambaram, A., Vorechovsky, I., Holmberg, E., Unden, A. B., Gillies, S., Negus, K., Smyth, I., Pressman, C., Leffell, D. J., Gerrard, B., Goldstein, A. M., Dean, M., Toftgard, R., Chenevix-Trench, G., Wainwright, B., and Bale, A. E. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell, 85: 841-851, 1996.
32. Oro, A. E., Higgins, K. M., Hu, Z. L., Bonifas, J. M., Epstein, E. H., and Scott, M. P. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science (Washington DC), 276: 817-821, 1997.
33. Goodrich, L. V., Milenkovic, L., Higgins, K. M., and Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science (Washington DC), 277: 1109-1113, 1997.
34. Hahn, H., Wojnowski, L., Zimmer, A. M., Hall, J., Miller, G., and Zimmer, A. Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Nat. Med., 4: 619-622, 1998.
35. Gailani, M. R., Stahle-Backdahl, M., Leffell, D. J., Glynn, M., Zaphiropoulos, P. G., Pressman, C., Unden, A. B., Dean, M., Brash, D. E., Bale, A. E., and Toftgard, R The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat. Genet., 14: 78-81, 1996.
36. Pietsch, T., Waha, A., Koch, A., Kraus, J., Albrecht, S., Tonn, J., Sorensen, N., Berthold, F., Henk, B., Schmandt, N., Wolf, H. K., Vondeimling, A., Wainwright, B., Chenevixtrench, G., Wiestler, O. D., and Wicking, C. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res., 57: 2085-2088, 1997.
37. Xie, J. W., Johnson, R. L, Zhang, X. L., Bare, J. W., Waldman, F. M., Cogen, P. H., Menon, A. G., Warren, R. S., Chen, L. C., Scott, M. P., and Epstein, E. H. Mutations of the patched gene in several types of sporadic extracutaneous tumors. Cancer Res., 57: 2369-2372, 1997.
38. Wolter, M., Reifenberger, J., Sommer, C., Ruzicka, T., and Reifenberger, G. Mutations in the human homologue of the Drosophila segment polarity gene patched (ptch) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res., 57: 2581-2585, 1997.
39. Ruppert, J. M., Vogelstein, B., and Kinzler, K. W. The zinc finger protein GLI transforms rodent cells in cooperation with adenovirus E1A. Mol. Cell. Biol., 11: 1724-1728, 1991.
40. Foster, K. W., Ren, S., Louro, I. D., Lobo-Ruppert, S. M., McKie-Bell, P., Grizzle, W., Hayes, M. R., Broker, T. R., Chow, L T., and Ruppert, J. M. Oncogene expression cloning by retroviral transduction of adenovirus E1a-immortalized rat Kidney RK3E cells: transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF. Cell Growth Differ., 10: 423-434, 1999.
41. Dilling, M. B., Dias, P., Shapiro, D. N., Germain, G. S., Johnson, R. K., and Houghton, P. J. Rapamycin selectively inhibits the growth of childhood rhabdomyosarcoma cells through inhibition of signaling via the type I insulin-like growth factor receptor. Cancer Res., 54: 903-907, 1994.
42. Hosoi, H., Dilling, M. B., Liu, L. N., Danks, M. K., Shikata, T., Sekulic, A., Abraham, R. T., Lawrence, J. C., and Houghton, P. J. Studies on the mechanism of resistance to rapamycin in human cancer cells. Mol. Pharmacol., 54: 815-824, 1998.
43. Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., and Snyder, S. H. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell, 78: 35-43, 1994.
44. Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., and Abraham, R. T. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J. Biol. Chem., 270: 815-822, 1995.
45. Brown, E. J., and Schreiber, S. L. A signaling pathway to translational control. Cell, 86: 517-520, 1996.
46. Barbet, N. C., Schneider, U., Helliwell, S. B., Stansfield, I., Tuite, M. F., and Hall, M. N. Tor controls translation initiation and early G1 progression in yeast. Mol. Biol. Cell, 7: 25-42, 1996.
47. Hoekstra, M. F. Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. Curr. Opin. Genet. Dev., 7: 170-175, 1997.
48. Thomas, G., and Hall, M. N. Tor signaling and control of cell growth. Curr. Opin. Cell Biol., 9: 782-787, 1997.
49. Hara, K., Yonezawa, K., Weng, Q. P., Kozlowski, M. T., Belham, C., and Avruch, J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and elF-4E BP1 through a common effector mechanism. J. Biol. Chem., 273: 14484-14494, 1998.
50. Chung, J., Kuo, C. J., Crabtree, G. R., and Blenis, J. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell, 69: 1227-1236, 1992.
51. Abraham, R. T., and Wiederrecht, G. J. Immunopharmacology of rapamycin. Annu. Rev. Immunol., 14: 483-510, 1996.
52. Gray, N. K., and Wickens, M. Control of translation initiation in animals. Annu. Rev. Cell Dev. Biol., 14: 399-458, 1998.
53. Jefferies, H. B., Reinhard, C., Kozma, S. C., and Thomas, G. Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family. Proc. Natl. Acad. Sci. USA, 31: 4441-4445, 1994.
54. Mendez, R., Myers, M. G., Jr., White, M. F., and Rhoads, R. E. Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-I phosphorylation by insulin requires insulin receptor substrate 1 and prtosphatidylinositol 3-kinase. Mol. Cell. Biol., 16: 2857-2864, 1996.
55. Terada, N., Patel, H. R., Takase, K., Kohno, K., Nairn, A. C., and Gelfand, E. W. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc. Natl. Acad. Sci. USA, 91: 11477-11481, 1994.
56. Pedersen, S., Cells, J. E., Nielsen, J., Christiansen, J., and Nielsen, F. C. Distinct repression of translation by wortmannin and rapamycin. Eur. J. Biochem., 247: 449-456, 1997.
57. Zaragoza, D., Ghavidel, A., Heitman, J., and Schultz, M. C. Hapamycin induces the G(0) program of transcriptional repression in yeast by interfering with the TOR signaling pathway. Mol. Cell. Biol., 18: 4463-4470, 1998.
58. Terada, N., Franklin, R. A., Lucas, J. J., Blenis, J., and Gelfand, E. W. Failure of rapamycin to block proliferation once resting cells have entered the cell cycle despite inactivation of p70 S6 kinase. J. Biol. Chem., 268: 12062-12068, 1993.
59. Seufferlein, T., and Rozengurt, E. Rapamycin inhibits constitutive p70S6K phosphorylation, cell proliferation, and colony formation in small cell lung cancer cells. Cancer Res., 56: 3895-3897, 1996.
60. Boyle, W. J., van der Geer, P., and Hunter, T. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol., 201: 110-149, 1991.
61. Brown, E. J., Beal, P. A., Keith, C. T., Chen, J., Shin, T. B., and Schreiber, S. L. Control of p70 S6 kinase by kinase activity of FRAP in vivo. Nature (Lomd.), 377: 441-446, 1995.
62. Chen, J., Zheng, X. F., Brown, E. J., and Schreiber, S. L. Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP 12-rapamycin-associated protein and characterization of a critical serine residue. Proc. Natl. Acad. Sci. USA, 92: 4947-4951, 1995.
63. von Manteuffel, S. R., Dennis, P. B., Pullen, N., Gingras, A. C., Sonenberg, N., and Thomas, G. The insulin-induced signaling pathway leading to S6 and initiation factor 4E binding protein 1 phosphorylation bifurcates at a rapamycin-sensitive point immediately upstream of p70S6K. Mol. Cell. Biol., 17: 5426-5436, 1997.
64. Scott, P. H., Brunn, G. J., Kohn, A. D., Roth, R. A., and Lawrence, J. C. Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc. Natl. Acad. Sci. USA, 95: 7772-7777, 1998.
65. Ruderman, J. V. MAP kinase and the activation of quiescent cells. Curr. Opin. Cell Biol., 5: 207-213, 1993.
66. Chung, J., Grammer, T. C., Lemon, K. P., Kazlauskas, A., and Blenis, J. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature (Lond.), 370: 71-75, 1994.
67. Ming, X. F., Burgering, B. M., Wennstrom, S., Claesson-Welsh, L., Heldin, C. H., Bos, J. L., Kozma, S. C., and Thomas, G. Activation of p70/p85 S6 kinase by a pathway independent of p21ras. Nature (Lond.), 371: 426-429, 1994.
68. de Groot, R. P., Schouten, G. J., de Wit, L, Ballou, L M., van der Eb, A. J., and Zantema, A. Induction of the mitogen-activated p70 S6 kinase by adenovirus E1A. Oncogene, 10: 543-548, 1995.
69. Downward, J. Regulating S6 kinase. Nature (Lond.), 371: 378-379, 1994.
70. Martel, J., Payet, M. D., and Dupuis, G. The MRD1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes. Leuk. Res., 21: 743-752, 1997.
71. Rawls, A., and Olson, E. N. MyoD meets its maker. Cell, 89: 5-8, 1997.
72. Wang-Wuu, S., Soukup, S., Ballard, E., Gotwals, B., and Lampkin, B. Chromosomal analysis of sixteen human rhabdomyosarcomas. Cancer Res., 48: 983-987, 1988.
73. Barr, F. G., Nauta, L E., Davis, R. J., Schafer, B. W., Nycum, L. M., and Biegel, J. A. In vivo amplification of the pax3-fkhr and pax7-fkhr fusion genes in alveolar rhabdomyosarcoma. Hum. Mol. Genet., 5: 15-21, 1996.
74. Biegel, J. A., Nycum, L. M., Valentine, V., Barr, F. G., and Shapiro, D. N. Detection of the t(2;13)(q35;q14) and pax3-fkhr fusion in alveolar rhabdomyosarcoma by fluorescence in situ hybridization. Genes Chromosomes Cancer, 12: 186-192, 1995.
75. Downing, J. R., Khandekar, A., Shurtleff, S. A., Head, D. R., Parham, D. M., Webber, B. L., Pappo, A. S., Hulshof, M. G., Conn, W. P., and Shapiro, D. N. Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma. Am. J. Pathol., 146: 626-634, 1995.
76. Sonenberg, N., and Gingras, A. C. The mRNA 5′ cap-binding protein elF4E and control of cell growth. Curr. Opin. Cell Biol., 10: 268-275, 1998.
77. Kleijn, M., Scheper, G. C., Voorma, H. O., and Thomas, A. A. Regulation of translation initiation factors by signal transaction. Eur. J. Biochem., 253: 531-544, 1998.
78. Hershey, J. W. Translational control in mammalian cells. Annu. Rev. Biochem., 60: 717-755, 1991.
79. Mendez, R., Kollmorgen, G., White, M. F., and Rhoads, R. E. Requirement of protein kinase C zeta for stimulation of protein synthesis by insulin. Mol. Cell. Biol., 17: 5184-5192, 1997.
80. Kimball, S. R., Horetsky, R. L., and Jefferson, L. S. Implication of elF2B rather than elF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts. J. Biol. Chem., 273: 30945-30953, 1998.
81. Marte, B. M., and Downward, J. PKB/AKT: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem. Sci., 22: 355-358, 1997.
82. Tlsty, T. D. A molecular blueprint for targeting cancer? Nat. Genet., 21: 64-65, 1999.
83. Myers, M. P., Pass, I., Batty, I. H., Vanderkaay, J., Stolarov, J. P., Hemmings, B. A., Wigler, M. H., Dowries, C. P., and Tonks, N. K. The lipid phosphatase activity of PTEN is critical for its tumor suppressor function. Proc. Natl. Acad. Sci. USA, 95: 13513-13518, 1998.
84. Stambolic, V., Suzuki, A., Delapompa, J. L., Brothers, G. M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J. M., Siderovski, D. P., and Mak, T. W. Negative regulation of PKB/AKT-dependent cell survival by the tumor suppressor PTEN. Cell, 95: 29-39, 1998.
85. Shayesteh, L., Lu, Y., Kuo, W-L., Baldocchi, R., Godfrey, T., Collins, C., Pinkel, D., Powell, B., Mills, G. B., and Gray, J. W. PIK3CA is implicated as an oncogene in ovarian cancer. Nat. Genet, 21: 99-102, 1999.
86. Cheng, J. Q., Godwin, A. K., Bellacosa, A., Taguchi, T., Franke, T. F., Hamilton, T. C., Tsichlis, P. N., and Testa, J. R. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc. Natl. Acad. Sci. USA, 89: 9267-9271, 1992.
87. Flynn, A., and Proud, C. G. The role of elF4 in cell proliferation. Cancer Surv., 27: 293-310, 1996.
88. Rousseau, D., Gingras, A. C., Pause, A., and Sonenberg, N. The elF4E-binding proteins 1 and 2 are negative regulators of cell growth. Oncogene, 13: 2415-2420, 1996.
89. Fukuchi-Shimogori, T., Ishii, I., Kashiwagi, K., Mashiba, H., Ekimoto, H., and Igarashi, K. Malignant transformation by overproduction of trans-lation initiation factor elF4G. Cancer Res., 57: 5041-5044, 1997.
90. Mateyak, M. K., Obaya, A. J., Adachi, S., and Sedivy, J. M. Pheno-types of c-myc-deficient rat fibroblasts isolated by targeted homologous recombination. Cell Growth Differ, 8: 1039-1048, 1997.
91. Deshane, J., Loechel, F., Conry, R. M., Siegal, G. P., King, C. R., and Curiel, D. T. Intracellular single-chain antibody directed against erbB2 down-regulates cell surface erbB2 and exhibits a selective anti-proliferative effect in erbB2 overexpressing cancer cell lines. Gene Therapy, 1: 332-337, 1994.
92. Vindelov, L. L., Christensen, I. J., and Nissen, N. I. A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry, 3: 323-327, 1983.
93. Lane, H. A., and Thomas, G. Purification and properties of mitogen-activated S6 kinase from rat liver and 3T3 cells. Methods Enzymol., 200: 268-291, 1991.
94. 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: 502-513, 1998.
95. Chomczynski, P., and Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem., 162: 156-159, 1987.