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This paper describes the identification the gene encoding Chico, a Drosophila insulin receptor substrate protein. Complete mutation of both copies of chico results in small but viable flies with reduced cell size and cell number. Mitotic clones of chico contain cells that are smaller than their heterozygous and wild-type neighbours. This paper provides further evidence for the role of an IGF/PI3K pathway in imaginal disc growth control.
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0032907439
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Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction
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The authors describe the phenotype of Lats1 knock-out mice. Mutation of Lats has multiple effects, including an increased frequency of soft-tissue sarcomas, ovarian stromal cell tumours and high sensitivity to carcinogens. In flies, all lats mutant tissues over-grow, whereas, in mice, only restricted Lats1 mutant tissues develop tumours. This paper, however, clearly demonstrates that a tumour suppressor identified in Drosophila has a tumour suppressor function in mammals.
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St John M.A., Tao W., Fei X., Fukumoto R., Carcangiu M.L., Brownstein D.G., Parlow A.F., McGrath J., Xu T. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat Genet. 21:1999;182-186. The authors describe the phenotype of Lats1 knock-out mice. Mutation of Lats has multiple effects, including an increased frequency of soft-tissue sarcomas, ovarian stromal cell tumours and high sensitivity to carcinogens. In flies, all lats mutant tissues over-grow, whereas, in mice, only restricted Lats1 mutant tissues develop tumours. This paper, however, clearly demonstrates that a tumour suppressor identified in Drosophila has a tumour suppressor function in mammals.
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St John, M.A.1
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38
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This paper describes the identification and biochemical characterisation of the human homologue of Lats, LATS1. LATS1 is phosphorylated and associates with CDC2 in early mitosis, thereby inhibiting CDC2 activity. Consistent with these observations, mutation of one copy of Drosophila cdc2 suppresses imaginal disc overgrowth induced by loss of lats. Thus cell-cycle control may be an important mechanism by which Lats suppresses tumour growth.
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Tao W., Zhang S., Turenchalk G.S., Stewart R.A., St John M.A., Chen W., Xu T. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat Genet. 21:1999;177-181. This paper describes the identification and biochemical characterisation of the human homologue of Lats, LATS1. LATS1 is phosphorylated and associates with CDC2 in early mitosis, thereby inhibiting CDC2 activity. Consistent with these observations, mutation of one copy of Drosophila cdc2 suppresses imaginal disc overgrowth induced by loss of lats. Thus cell-cycle control may be an important mechanism by which Lats suppresses tumour growth.
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Tao, W.1
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39
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This paper shows that cells mutant for gigas, the Drosophila homologue of the tuberous sclerosis complex gene-2 (TSC2), are larger than surrounding heterozygous and wild-type cells. The gigas mutant cells replicate their DNA without division, which presumably enables them to increase in size. Although greatly increased in size, gigas mutant cells can still differentiate. When large gigas mutant clones were generated, the imaginal discs became enlarged, though this effect was accompanied by an extension of the larval period. The Drosophila homologue of the TSC1 gene is also identified.
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Ito N., Rubin G.M. gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell. 96:1999;529-539. This paper shows that cells mutant for gigas, the Drosophila homologue of the tuberous sclerosis complex gene-2 (TSC2), are larger than surrounding heterozygous and wild-type cells. The gigas mutant cells replicate their DNA without division, which presumably enables them to increase in size. Although greatly increased in size, gigas mutant cells can still differentiate. When large gigas mutant clones were generated, the imaginal discs became enlarged, though this effect was accompanied by an extension of the larval period. The Drosophila homologue of the TSC1 gene is also identified.
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