The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila

Genes and Development

Volumn 18, Issue 23, 2004, Pages 2879-2892

  Reiling, Jan H ^a   Hafen, Ernst ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Hypoxia; Insulin signaling; REDD1; RTP801; S6 kinase; TSC

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1;

ARTICLE; CONTROLLED STUDY; DROSOPHILA; ENZYME ACTIVITY; GENE OVEREXPRESSION; HYPOXIA; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SEQUENCE HOMOLOGY;

AMINO ACID SEQUENCE; ANIMALS; ANOXIA; BLOTTING, WESTERN; DROSOPHILA; DROSOPHILA PROTEINS; MOLECULAR SEQUENCE DATA; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RIBOSOMAL PROTEIN S6 KINASES; SEQUENCE HOMOLOGY, AMINO ACID;

MAMMALIA; SCYLLA; TOR;

EID: 10044276784     PISSN: 08909369     EISSN: None     Source Type: Journal    
DOI: 10.1101/gad.322704     Document Type: Article

References (69)

1. Andjelkovic, M., Jones, P.P., Grossniklaus, U., Cron, P., Schier, A.F., Dick, M., Bilbe, G., and Hemmings, B.A. 1995. Developmental regulation of expression and activity of multiple forms of the Drosophila RAC protein kinase. J. Biol. Chem. 270: 4066-4075.
2. Arsham, A.M., Howell, J.J., and Simon, M.C. 2003. A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J. Biol. Chem. 278: 29655-29660.
3. Azevedo, R.B., French, V., and Partridge, L. 2002. Temperature modulates epidermal cell size in Drosophila melanogaster. J. Insect Physiol 48: 231-237.
4. Basler, K., Christen, B., and Hafen, E. 1991. Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye. Cell 64: 1069-1081.
5. Bernal, A. and Kimbrell, D.A. 2000. Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity. Proc. Natl. Acad. Sci. 97: 6019-6024.
6. Bohni, R., Riesgo-Escovar, J., Oldham, S., Brogiolo, W., Stocker, H., Andruss, B.F., Beckingham, K., and Hafen, E. 1999. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97: 865-875.
7. Brand, A.H. and Perrimon, N. 1993. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401-415.
8. Brogiolo, W., Stocker, H., Ikeya, T., Rintelen, F., Fernandez, R., and Hafen, E. 2001, An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr. Biol. 11: 213-221.
9. Brugarolas, J.B., Vazquez, F., Reddy, A., Sellers, W.R., and Kaelin Jr., W.G. 2003. TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 4: 147-158.
10. Brugarolas, J., Lei, K., Hurley, R.L., Manning, B.D., Reiling, J.H., Hafen, E., Witters, L.A., Ellisen, L.W., and Kaelin Jr., W.G. 2004. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes & Dev. (this issue).
11. Bruick, R.K. 2003. Oxygen sensing in the hypoxic response pathway: Regulation of the hypoxia-inducible transcription factor. Genes & Dev. 17: 2614-2623.
12. Carling, D. 2004. The AMP-activated protein kinase cascade - A unifying system for energy control. Trends Biochem. Sci. 29: 18-24.
13. Cho, K.S., Lee, J.H., Kim, S., Kim, D., Koh, H., Lee, J., Kim, C., Kim, J., and Chung, J. 2001. Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway. Proc. Natl. Acad. Sci. 98: 6144-6149.
14. Ellisen, L.W., Ramsayer, K.D., Johannessen, C.M., Yang, A., Beppu, H., Minda, K., Oliner, J.D., McKeon, F., and Haber, D.A. 2002. REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species. Mol. Cell 10: 995-1005.
15. Frazier, M.R., Woods, H.A., and Harrison, J.F. 2001. Interactive effects of rearing temperature and oxygen on the development of Drosophila melanogaster. Physiol. Biochem. Zool. 74: 641-650.
16. Frei, C. and Edgar, B.A. 2004. Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell growth. Dev. Cell 6: 241-251.
17. Gao, X. and Pan, D. 2001. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes & Dev. 15: 1383-1392.
18. Gao, X., Neufeld, T.P., and Pan, D. 2000. Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev. Biol. 221: 404-418.
19. Gao, X., Zhang, Y., Arrazola, P., Hino, O., Kobayashi, T., Yeung, R.S., Ru, B., and Pan, D. 2002. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat. Cell Biol. 4: 699-704.
20. Garami, A., Zwartkruis, F.J., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S.C., Hafen, E., Bos, J.L., and Thomas, G. 2003. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol. Cell 11: 1457-1466.
21. Garofalo, R.S. 2002. Genetic analysis of insulin signaling in Drosophila. Trends Endocrinol. Metab. 13: 156-162.
22. Gingras, A.C., Raught, B., and Sonenberg, N. 2004. mTOR signaling to translation. Curr. Top. Microbiol. Immunol. 279: 169-197.
23. Goberdhan, D.C., Paricio, N., Goodman, E.C., Mlodzik, M., and Wilson, C. 1999. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes &. Dev. 13: 3244-3258.
24. Hay, N. and Sonenberg, N. 2004. Upstream and downstream of mTOR. Genes & Dev. 18: 1926-1945.
25. Huang, H., Potter, C.J., Tao, W., Li, D.M., Brogiolo, W., Hafen, E., Sun, H., and Xu, T. 1999. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development 126: 5365-5372.
26. Ikeya, T., Galic, M., Belawat, P., Nairz, K., and Hafen, E. 2002. Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Curr. Biol. 12: 1293-1300.
27. Inoki, K., Li, Y., Zhu, T., Wu, J., and Guan, K.L. 2002. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4: 648-657.
28. Inoki, K., Li, Y., Xu, T., and Guan, K.L. 2003a. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes & Dev. 17: 1829-1834.
29. Inoki, K., Zhu, T., and Guan, K.L. 2003b. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115: 577-590.
30. Ito, N. and Rubin, G.M. 1999. gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell 96: 529-539.
31. Jacinto, E. and Hall, M.N. 2003. Tor signalling in bugs, brain and brawn. Nat. Rev. Mol. Cell. Biol. 4: 117-126.
32. Junger, M.A., Rintelen, F., Stocker, H., Wasserman, J.D., Vegh, M., Radimerski, T., Greenberg, M.E., and Hafen, E. 2003. The Drosophila Forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J. Biol. 2: 7.
33. Kimura, N., Tokunaga, C., Dalal, S., Richardson, C., Yoshino, K., Hara, K., Kemp, B.E., Witters, L.A., Mimura, O., and Yonezawa, K. 2003. A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway. Genes Cells 8: 65-79.
34. Lavista-Llanos, S., Centanin, L., Irisarri, M., Russo, D.M., Gleadle, J.M., Bocca, S.N., Muzzopappa, M., Ratcliffe, P.J., and Wappner, P. 2002. Control of the hypoxic response in Drosophila melanogaster by the basic helix-loop-helix PAS protein similar. Mol. Cell. Biol. 22: 6842-6853.
35. Leevers, S.J., Weinkove, D., MacDougall, L.K., Hafen, E., and Waterfield, M.D. 1996. The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J. 15: 6584-6594.
36. Lehmann, R. and Tautz, D. 1994. In situ hybridization to RNA. Methods Cell. Biol. 44: 575-598.
37. Majumder, P.K., Febbo, P.G., Bikoff, R., Berger, R., Xue, Q., McMahon, L.M., Manola, J., Brugarolas, J., McDonnell, T.J., Golub, T.R., et al. 2004. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat. Med. 10: 594-601.
38. 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.
39. Montagne, J., Stewart, M.J., Stocker, H., Hafen, E., Kozma, S.C., and Thomas, G. 1999. Drosophila S6 kinase: A regulator of cell size. Science 285: 2126-2129.
40. Morin, X., Daneman, R., Zavortink, M., and Chia, W. 2001. A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila. Proc. Natl. Acad. Sci. 98: 15050-15055.
41. Neshat, M.S., Mellinghoff, I.K., Tran, C., Stiles, B., Thomas, G., Petersen, R., Frost, P., Gibbons, J.J., Wu, H., and Sawyers, C.L. 2001. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc. Natl. Acad. Sci. 98: 10314-10319.
42. Newsome, T.P., Asling, B., and Dickson, B.J. 2000. Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development 127: 851-860.
43. Oldham, S., Montagne, J., Radimerski, T., Thomas, G., and Hafen, E. 2000. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes & Dev. 14: 2689-2694.
44. Oldham, S., Stocker, H., Laffargue, M., Wittwer, F., Wymann, M., and Hafen, E. 2002. The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development 129: 4103-4109.
45. O'Neill J.W. and Bier, E. 1994. Double-label in situ hybridization using biotin and digoxigenin-tagged RNA probes. Biotechniques 17: 870, 874-875.
46. Palos, L.A. and Blasko, G. 1979. Effect of hypoxia on the development of Drosophila melanogaster (Meigen). Aviat. Space Environ. Med. 50: 411-412.
47. Pan, D., Dong, J., Zhang, Y., and Gao, X. 2004. Tuberous sclerosis complex: From Drosophila to human disease. Trends Cell Biol. 14: 78-85.
48. -/- mice exhibit perinatal lethality and rapamycin-sensitive 5′-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway. Mol. Cell. Biol. 24: 3112-3124.
49. +/- mice. Proc. Natl. Acad. Sci. 98: 10320-10325.
50. Potter, C.J., Huang, H., and Xu, T. 2001. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105: 357-368.
51. Radimerski, T., Montagne, J., Hemmings-Mieszczak, M., and Thomas, G. 2002a. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes & Dev. 16: 2627-2632.
52. Radimerski, T., Montagne, J., Rintelen, F., Stocker, H., van der Kaay, J., Downes, C.P., Hafen, E., and Thomas, G. 2002b. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat. Cell. Biol. 4: 251-255.
53. Rintelen, F., Stocker, H., Thomas, G., and Hafen, E. 2001. PDK1 regulates growth through Akt and S6K in Drosophila. Proc. Natl. Acad. Sci. 98: 15020-15025.
54. Rorth, P. 1996. A modular misexpression screen in Drosophila detecting tissue-specific phenotypes. Proc. Natl. Acad. Sci. 93: 12418-12422.
55. Safran, M. and Kaelin Jr., W.G. 2003. HIF hydroxylation and the mammalian oxygen-sensing pathway. J. Clin. Invest. 111: 779-783.
56. Saucedo, L.J., Gao, X., Chiarelli, D.A., Li, L., Pan, D., and Edgar, B.A. 2003. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol. 5: 566-571.
57. Shi, Y., Gera, J., Hu, L., Hsu, J.H., Bookstein, R., Li, W., and Lichtenstein, A. 2002. Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779. Cancer Res. 62: 5027-5034.
58. Shoshani, T., Faerman, A., Mett, I., Zelin, E., Tenne, T., Gorodin, S., Moshel, Y., Elbaz, S., Budanov, A., Chajut, A., et al. 2002. Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis. Mol. Cell. Biol. 22: 2283-2293.
59. Stocker, H., Andjelkovic, M., Oldham, S., Laffargue, M., Wymann, M.P., Hemmings, B.A., and Hafen, E. 2002. Living with lethal PIP3 levels: Viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science 295: 2088-2091.
60. Stocker, H., Radimerski, T., Schindelholz, B., Wittwer, F., Belawat, P., Daram, P., Breuer, S., Thomas, G., and Hafen, E. 2003. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat. Cell Biol. 5: 559-565.
61. Stolovich, M., Tang, H., Hornstein, E., Levy, G., Cohen, R., Bae, S.S., Birnbaum, M.J., and Meyuhas, O. 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.
62. Sulis, M.L. and Parsons, R. 2003. PTEN: From pathology to biology. Trends Cell Biol. 13: 478-483.
63. Tang, H., Hornstein, E., Stolovich, M., Levy, G., Livingstone, M., Templeton, D., Avruch, J., and Meyuhas, O. 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.
64. Tapon, N., Ito, N., Dickson, B.J., Treisman, J.E., and Hariharan, I.K. 2001. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105: 345-355.
65. Tee, A.R., Manning, B.D., Roux, P.P., Cantley, L.C., and Blenis, J. 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.
66. Wang, Z., Malone, M.H., Thomenius, M.J., Zhong, F., Xu, F., and Distelhorst, C.W. 2003. Dexamethasone-induced gene 2 (dig2) is a novel pro-survival stress gene induced rapidly by diverse apoptotic signals. J. Biol. Chem. 278: 27053-27058.
67. Zhang, H., Stallock, J.P., Ng, J.C., Reinhard, C., and Neufeld, T.P. 2000. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes & Dev. 14: 2712-2724.
68. Zhang, Y., Gao, X., Saucedo, L.J., Ru, B., Edgar, B.A., and Pan, D. 2003. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 5: 578-581.
69. Zinke, I., Schutz, C.S., Katzenberger, J.D., Bauer, M., and Pankratz, M.J. 2002. Nutrient control of gene expression in Drosophila: Microarray analysis of starvation and sugar-dependent response. EMBO J. 21: 6162-6173.