INDUCTION OF APOPTOSIS BY THE MOUSE NEDD2 GENE, WHICH ENCODES A PROTEIN SIMILAR TO THE PRODUCT OF THE CAENORHABDITIS-ELEGANS CELL-DEATH GENE CED-3 AND THE MAMMALIAN IL-1-BETA-CONVERTING ENZYME
INDUCTION OF APOPTOSIS BY THE MOUSE NEDD2 GENE, WHICH ENCODES A PROTEIN SIMILAR TO THE PRODUCT OF THE CAENORHABDITIS-ELEGANS CELL-DEATH GENE CED-3 AND THE MAMMALIAN IL-1-BETA-CONVERTING ENZYME
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DOI：
10.1101/gad.8.14.1613
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发表时间：
1994-07-15
影响因子：
10.5
通讯作者：
JENKINS, NA
中科院分区：
文献类型：
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作者：
KUMAR, S;KINOSHITA, M;JENKINS, NA
通过减法克隆，我们先前鉴定了一组小鼠基因（命名为Nedd1至Nedd10）在大脑中表达下调。我们现在发现，其中一个基因Nedd2编码一种类似于哺乳动物白细胞介素-1 β转换酶（ICE）的蛋白质，也是秀丽隐杆线虫细胞死亡基因ced-3 （ced-3）的产物。已知ICE和CED-3编码假定的半胱氨酸蛋白酶，并在培养细胞中过度表达时诱导细胞凋亡。在培养的成纤维细胞和神经母细胞瘤细胞中，过表达Nedd2也会导致细胞凋亡死亡，这种凋亡被人bcl-2基因的表达所抑制，这表明Nedd2在功能上与秀丽隐杆线虫的ced-3基因相似。我们还发现，在胚胎发育过程中，Nedd2在几种程序性细胞死亡率高的小鼠组织（如中枢神经系统和肾脏）中高度表达。我们的数据表明，Nedd2是哺乳动物程序性细胞死亡机制的重要组成部分。
By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery.