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


, : The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes & Development 18(23): 2879-2892

Diverse extrinsic and intrinsic cues must be integrated within a developing organism to ensure appropriate growth at the cellular and organismal level. In Drosophila, the insulin receptor/TOR/S6K signaling network plays a fundamental role in the control of metabolism and cell growth. Here we show that scylla and charybdis, two homologous genes identified as growth suppressors in an EP (enhancer/promoter) overexpression screen, act as negative regulators of growth. The simultaneous loss of both genes generates flies that are more susceptible to reduced oxygen concentrations (hypoxia) and that show mild overgrowth phenotypes. Conversely, scylla or charybdis overactivation reduces growth. Growth inhibition is associated with a reduction in S6K but not PKB/Akt activity. Together, genetic and biochemical analysis places Scylla/Charybdis downstream of PKB and upstream of TSC. Furthermore, we show that scylla and charybdis are induced under hypoxic conditions and that scylla is a target of Drosophila HIF-1 (hypoxia-inducible factor-1) like its mammalian counterpart RTP801/REDD1, thus establishing a potential cross-talk between growth and oxygen sensing.

US$19.90

PMID: 15545626

DOI: 10.1101/gad.322704


Other references

Bail, H.J.; Kolbeck, S.; Lindner, T.; Dahne, M.; Weiler, A.; Windhagen, H.J.; Raun, K.; Skjaerbaek, C.; Flyvbjerg, A.; Ørskov, H.; Haas, N.P.; Raschke, M.J., 2001: The effect of growth hormone on insulin-like growth factor I and bone metabolism in distraction osteogenesis. Limb lengthening in the left tibia of 30 mature female Yucatan micropigs was performed using distraction osteogenesis. A treatment group of 15 animals received recombinant porcine growth hormone (r-pGH) (100 microg/kg/day) while the others served...

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Prestwich, G.D., 2004: Phosphoinositide signaling; from affinity probes to pharmaceutical targets. Lipid signaling by phosphoinositides (PIP(n)s) involves an array of proteins with lipid recognition, kinase, phosphatase, and phospholipase functions. Understanding PIP(n) pathway signaling requires identification and characterization of PIP(n)-in...

Voss H.J.; Holtz W., 1984: Estrus synchronization in dairy heifers using different compounds. On 47 dairy farms near Goettingen 392 German Black and White and 74 German Red and White heifers were synchronized with either 1 of the prostaglandins Estrumate (ES) and Dinolytic (DY) or one of the gestagens (PRID) and Norgestomet (NOR). Followin...

Ma, M.T.; Karas, J.A.; White, J.M.; Scanlon, D.; Donnelly, P.S., 2009: A new bifunctional chelator for copper radiopharmaceuticals: a cage amine ligand with a carboxylate functional group for conjugation to peptides. A new sarcophagine cage amine ligand with a pendent carboxylate functional group has been synthesised; the ligand has been conjugated to tumour targeting peptides ([Tyr3]-octreotate and [Lys3]-bombesin) and the conjugates radiolabelled with copper...

Munro-Ashman, D., 1968: Some aspects of dermatology. 7. Contact dermatitis as a nursing hazard. Nursing Times 64(29): 974-976

Lopez Berestein G.; Reuben J.; Hersh E.M.; Kilbourn R.; Hester J.P.; Bielski M.; Talpaz M.; Mavligit G.M., 1983: Comparative functional analysis of lymphocytes and monocytes from plateletpheresis. Large numbers (2.9 .+-. 1.2 .times. 109) of mononuclear cells can be obtained from incidental samples collected during routine plateletpheresis. Studies comparing characteristics and functions of mononuclear cells derived from venous blood samples...

Reynolds J., 1969: Emergent transfusion therapy. Sharpe, John C And Frederick W Marx, Jr (Edited By) Management Of Medical Emergencies 2nd Ed Xv + 756p Illus Mcgraw-Hill Book Co : New York , U S A And London, England 465-471

Dupuis., 1900: Notes sur quelques Cicindeles provenant de Tunisie. Annales de la Societe Entomologique de Belgique, 54 187-195

Raitviir, A., 1977: Some new species of dasyscyphus. D. sinegoricus, D. lespedezae and D. ponticus are described as new species from the USSR.