Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation
Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation
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DOI：
10.1038/sj.emboj.7601484
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发表时间：
2007-01-24
期刊：
影响因子：
11.4
通讯作者：
Jasper, Heinrich
中科院分区：
文献类型：
--
作者：
Luo, Xi;Puig, Oscar;Jasper, Heinrich
在后生动物中，被环境损伤的细胞必须被修复或清除，以确保组织的稳态。最近的研究表明，细胞存活信号和促凋亡刺激之间的平衡控制着细胞修复和死亡的决定。这些相互竞争的信号如何被整合和解释以实现对体内细胞命运的精确控制尚不完全清楚。在这里，我们发现叉头盒O转录因子Foxo和AP-1转录因子DFos是jun - n末端激酶信号传导的下游所必需的，在发育中的果蝇视网膜中对紫外线诱导的DNA损伤的凋亡反应中。这两种转录因子均调控促凋亡基因的表达。我们的研究结果表明，紫外线诱导的细胞凋亡可以通过受体酪氨酸激酶介导的Foxo失活来抑制。这些数据表明，通过Foxo整合应激和生存信号驱动了细胞死亡和体内受损细胞修复之间的决定。
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.