A Drosophila model to study the functions of TWIST orthologs in apoptosis and proliferation.
The twist gene has been characterized for its role in myogenesis in several species. In addition, in mammalian cultured cells, it has been shown that twist is a potential oncogene antagonizing p53-dependent apoptosis. To study, in vivo, the role of twist in apoptosis and proliferation, we constructed transgenic Drosophila lines allowing ectopic expression of different twist orthologs. We report that: (i) Drosophila twist induces apoptosis and activates the reaper promoter, (ii) nematode twist induces arrest of proliferation without apoptosis, and (iii) human twist retains its potentialities observed in mammalian cultured cells and antagonizes Drosophila p53-dependent apoptosis. In addition, we show that human twist is able to induce cell proliferation in Drosophila. Data suggest that the pathway by which human twist antagonizes Drosophila p53 could be conserved. These transgenic lines thus constitute a powerful tool to identify targets and modifiers of human twist.
Gullaud
M
M
Institut Jacques Monod, Tour43, 2, Place Jussieu, 75005 Paris, France.
Delanoue
R
R
Silber
J
J
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051879:Twist-Related Protein 1
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C086973:rpr protein, Drosophila; D007334:Insulin-Like Growth Factor I