title: Different cell cycle modifications repress apoptosis at different steps independent of developmental signaling in Drosophila.
abstract: Apoptotic cell death is important for the normal development of a variety of organisms. Apoptosis is also a response to DNA damage and an important barrier to oncogenesis. The apoptotic response to DNA damage is dampened in specific cell types during development. Developmental signaling pathways can repress apoptosis, and reduced cell proliferation also correlates with a lower apoptotic response. However, because developmental signaling regulates both cell proliferation and apoptosis, the relative contribution of cell division to the apoptotic response has been hard to discern in vivo. Here we use Drosophila oogenesis as an in vivo model system to determine the extent to which cell proliferation influences the apoptotic response to DNA damage. We find that different types of cell cycle modifications are sufficient to repress the apoptotic response to ionizing radiation independent of developmental signaling. The step(s) at which the apoptosis pathway was repressed depended on the type of cell cycle modification-either upstream or downstream of expression of the p53-regulated proapoptotic genes. Our findings have important implications for understanding the coordination of cell proliferation with the apoptotic response in development and disease, including cancer and the tissue-specific responses to radiation therapy.
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405.
authors.forename: Suozhi
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405 bcalvi@indiana.edu.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Calvi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology* / Q000528:radiation effects; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002455:Cell Division; D049109:Cell Proliferation / Q000235:genetics / Q000528:radiation effects; D019927:Cyclin E / Q000378:metabolism; D004249:DNA Damage; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D011839:Radiation, Ionizing; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019927:Cyclin E; D029721:Drosophila Proteins; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase