A genome-wide RNAi screen reveals multiple regulators of caspase activation.
A genome-wide RNAi screen reveals multiple regulators of caspase activation.
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DOI：
10.1083/jcb.200708090
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发表时间：
2007-11-19
期刊：
影响因子：
--
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Yi CH;Sogah DK;Boyce M;Degterev A;Christofferson DE;Yuan J
细胞凋亡是一种进化上保守的细胞自杀机制，可以在各种应激刺激下被激活。越来越多的证据表明，细胞凋亡调控依赖于专门的细胞死亡信号通路，也整合了来自其他调控回路的不同信号，包括细胞内稳态的信号。我们提出了一个全基因组RNA干扰筛选系统地确定果蝇细胞DNA损伤诱导的细胞凋亡的调节因子。我们鉴定了47个双链RNA，它们靶向功能多样的基因组，包括几个在促进细胞死亡中具有已知功能的基因。进一步的表征揭示了10个基因，影响半胱天冬酶激活后，去除果蝇细胞凋亡抑制剂1。这一组包括果蝇启动子胱天蛋白酶Dronc，令人惊讶的是，几种代谢调节剂，候选肿瘤抑制剂Charlatan和N-乙酰转移酶ARD 1。重要的是，这些基因中的几个在调节哺乳动物细胞凋亡中显示出功能保守性。我们的数据表明，以前不受重视的各种细胞过程和半胱天冬酶依赖性细胞死亡之间的基本连接。
Apoptosis is an evolutionally conserved cellular suicide mechanism that can be activated in response to a variety of stressful stimuli. Increasing evidence suggests that apoptotic regulation relies on specialized cell death signaling pathways and also integrates diverse signals from additional regulatory circuits, including those of cellular homeostasis. We present a genome-wide RNA interference screen to systematically identify regulators of apoptosis induced by DNA damage in Drosophila melanogaster cells. We identify 47 double- stranded RNA that target a functionally diverse set of genes, including several with a known function in promoting cell death. Further characterization uncovers 10 genes that influence caspase activation upon the removal of Drosophila inhibitor of apoptosis 1. This set includes the Drosophila initiator caspase Dronc and, surprisingly, several metabolic regulators, a candidate tumor suppressor, Charlatan, and an N-acetyltransferase, ARD1. Importantly, several of these genes show functional conservation in regulating apoptosis in mammalian cells. Our data suggest a previously unappreciated fundamental connection between various cellular processes and caspase-dependent cell death.
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