Different cell cycle modifications repress apoptosis at different steps independent of developmental signaling in Drosophila.
Different cell cycle modifications repress apoptosis at different steps independent of developmental signaling in Drosophila.
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DOI：
10.1091/mbc.e16-03-0139
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发表时间：
2016-06-15
影响因子：
3.3
通讯作者：
Calvi BR
中科院分区：
文献类型：
--
作者：
Qi S;Calvi BR
细胞周期的基因操作抑制细胞凋亡，而不依赖于发育信号。这些发现对于理解细胞增殖和凋亡在发育和疾病中的协调具有更广泛的相关性。细胞凋亡性死亡对多种生物体的正常发育具有重要意义。细胞凋亡也是对DNA损伤的一种反应，也是肿瘤发生的重要屏障。在发育过程中，对DNA损伤的凋亡反应在特定类型的细胞中受到抑制。发育中的信号通路可以抑制细胞凋亡，细胞增殖减少也与较低的凋亡反应相关。然而，由于发育信号既调节细胞增殖又调节细胞凋亡，在体内很难辨别细胞分裂对凋亡反应的相对贡献。在这里，我们使用果蝇卵子发生作为体内模型系统来确定细胞增殖对DNA损伤的凋亡反应的影响程度。我们发现，不同类型的细胞周期修饰足以抑制对电离辐射的凋亡反应，而不依赖于发育信号。细胞凋亡途径被抑制的步骤(S)取决于细胞周期修饰的类型--P53调节的促凋亡基因表达的上游或下游。我们的发现对于理解细胞增殖与细胞凋亡反应在发育和疾病(包括癌症和放射治疗的组织特异性反应)中的协调具有重要意义。
Genetic manipulations of the cell cycle repress apoptosis independent of developmental signaling. The findings have broader relevance to understanding the coordination of cell proliferation and apoptosis in development and disease. 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.