Drosophila E2F1 has context-specific pro- and antiapoptotic properties during development
Drosophila E2F1 has context-specific pro- and antiapoptotic properties during development
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DOI：
10.1016/j.devcel.2005.08.015
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发表时间：
2005-10-01
影响因子：
11.8
通讯作者：
Dyson, NJ
中科院分区：
文献类型：
--
作者：
Moon, NS;Frolov, MV;Dyson, NJ
E2F转录因子通常被认为是细胞凋亡的正调节因子。在这项研究中，我们证明 dE2F1 和 dDP 对于果蝇翼盘 DNA 损伤诱导细胞凋亡的正常模式很重要。出乎意料的是，E2F 所发挥的作用根据细胞在椎间盘内的位置而变化。在受辐射的野生型椎间盘中，介入细胞表现出高水平的 DNA 损伤诱导的细胞凋亡，而 D/V 边界内的细胞受到保护。在缺乏 E2F 调节的受辐射椎间盘中，介入细胞在很大程度上受到保护，但在 D/V 边界发现凋亡细胞。 E2F 在 D/V 边界处的保护作用是由于在 hid 抑制中的空间限制作用。这些功能丧失实验表明，E2F 不能简单地归类为促凋亡因子或抗凋亡因子。相反，E2F 在损伤反应中的总体作用差异很大，并且取决于细胞环境。
E2F transcription factors are generally believed to be positive regulators of apoptosis. In this study, we show that dE2F1 and dDP are important for the normal pattern of DNA damage-induced apoptosis in Drosophila wing discs. Unexpectedly, the role that E2F plays varies depending on the position of the cells within the disc. In irradiated wild-type discs, intervein cells show a high level of DNA damage-induced apoptosis, while cells within the D/V boundary are protected. In irradiated discs lacking E2F regulation, intervein cells are largely protected, but apoptotic cells are found at the D/V boundary. The protective effect of E2F at the D/V boundary is due to a spatially restricted role in the repression of hid. These loss-of-function experiments demonstrate that E2F cannot be classified simply as a pro- or antiapoptotic factor. Instead, the overall role of E2F in the damage response varies greatly and depends on the cellular context.