Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation.
Cells damaged by environmental insults have to be repaired or eliminated to ensure tissue homeostasis in metazoans. Recent studies suggest that the balance between cell survival signals and pro-apoptotic stimuli controls the decision between cell repair and death. How these competing signals are integrated and interpreted to achieve accurate control over cell fate in vivo is incompletely understood. Here, we show that the Forkhead Box O transcription factor Foxo and the AP-1 transcription factor DFos are required downstream of Jun-N-terminal kinase signaling for the apoptotic response to UV-induced DNA damage in the developing Drosophila retina. Both transcription factors regulate the pro-apoptotic gene hid. Our results indicate that UV-induced apoptosis is repressed by receptor tyrosine kinase-mediated inactivation of Foxo. These data suggest that integrating stress and survival signals through Foxo drives the decision between cell death and repair of damaged cells in vivo.
Luo
Xi
X
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Puig
Oscar
O
Hyun
Joogyung
J
Bohmann
Dirk
D
Jasper
Heinrich
H
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian; D005260:Female; D051858:Forkhead Transcription Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D048670:MAP Kinase Kinase 4 / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009479:Neuropeptides / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000528:radiation effects; D014158:Transcription, Genetic; D014466:Ultraviolet Rays / Q000009:adverse effects*
D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; C108880:HID protein, Drosophila; D009479:Neuropeptides; C435749:kay protein, Drosophila; D048670:MAP Kinase Kinase 4