Ras promotes cell survival in Drosophila by downregulating hid expression.
Activation of Ras inhibits apoptosis during Drosophila development. Genetic evidence indicates that Ras antiapoptotic activity in the developing eye is regulated by the Drosophila EGF receptor and operates through the Raf/MAPK pathway. Decreased activity of this pathway enhances, and increased activity suppresses, apoptosis induced by ectopic expression of the cell death regulators reaper (rpr) and head involution defective (hid). In addition, ectopic activation of the Ras/MAPK pathway in the developing embryo and in the developing eye suppresses naturally occurring apoptosis and regulates the transcription of the proapoptotic gene hid. Null alleles of hid recapitulate the antiapoptotic activities of Ras/MAPK, providing genetic evidence that downregulation of hid is an important mechanism by which Ras promotes survival.
Kurada
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Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
White
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K
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases; D005123:Eye / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009419:Nerve Tissue Proteins; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D018010:Receptors, Invertebrate Peptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
C076188:AOP protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; C108880:HID protein, Drosophila; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010455:Peptides; D011518:Proto-Oncogene Proteins; D018010:Receptors, Invertebrate Peptide; D012097:Repressor Proteins; D014157:Transcription Factors; C083884:pnt protein, Drosophila; C086973:rpr protein, Drosophila; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C086795:rl protein, Drosophila; D018631:ras Proteins