Shigenaga A, Funahashi Y, Kimura K, Kobayakawa Y, Kamada S, Tsujimoto Y, Tanimura T
Department of Biology, Faculty of Science, Kyushu University, Ropponmatsu, Fukuoka 810, Japan.
Cell Death Differ. 1997 Jul;4(5):371-7. doi: 10.1038/sj.cdd.4400254.
CED-3 is a cysteine protease required for programmed cell death in the nematode, Caenorhabditis elegans, and shares a sequence similarity with mammalian ICE (interleukin-1beta converting enzyme) family proteases. Both CED-3 and ICE family proteases can induce programmed cell death in mammalian cells. Structural and functional similarities between CED-3 and ICE family proteases indicate that the mechanism of cell death is evolutionarily conserved, suggesting the presence of a similar mechanism involving CED-3/ICE-like proteases in Drosophila. Here we determined whether CED-3 or ICE functions to induce programmed cell death in Drosophila. We have generated transformant lines in which ced-3 or Ice is ectopically expressed using the GAL4-UAS system. Expression of CED-3 and ICE can elicit cell death in Drosophila and the cell death was blocked by coexpressing the p35 gene which encodes a viral inhibitor of CED-3/ICE proteases. Results support the idea that the mechanism of programmed cell death controlled by CED-3/ICE is conserved among widely divergent animal species including Drosophila, and the system described provides a tool to dissect cell death mechanism downstream of CED-3/ICE proteases.
CED-3是线虫秀丽隐杆线虫程序性细胞死亡所需的一种半胱氨酸蛋白酶，与哺乳动物的ICE（白细胞介素-1β转化酶）家族蛋白酶具有序列相似性。CED-3和ICE家族蛋白酶都能在哺乳动物细胞中诱导程序性细胞死亡。CED-3和ICE家族蛋白酶之间的结构和功能相似性表明细胞死亡机制在进化上是保守的，这表明果蝇中存在一种涉及CED-3/ICE样蛋白酶的类似机制。在这里，我们确定了CED-3或ICE是否在果蝇中发挥诱导程序性细胞死亡的作用。我们利用GAL4-UAS系统构建了ced-3或Ice异位表达的转化株系。CED-3和ICE的表达可在果蝇中引发细胞死亡，并且通过共表达编码CED-3/ICE蛋白酶病毒抑制剂的p35基因可阻断细胞死亡。结果支持了这样一种观点，即由CED-3/ICE控制的程序性细胞死亡机制在包括果蝇在内的广泛不同的动物物种中是保守的，并且所描述的系统提供了一种剖析CED-3/ICE蛋白酶下游细胞死亡机制的工具。
