Hengartner M O, Horvitz H R
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Cell. 1994 Feb 25;76(4):665-76. doi: 10.1016/0092-8674(94)90506-1.
The activity of the C. elegans gene ced-9 is required to protect cells that normally survive from undergoing programmed cell death. Here we describe the cloning and molecular characterization of this gene. ced-9 is an element of a polycistronic locus that also contains the gene cyt-1, which encodes a protein similar to cytochrome b560 of complex II of the mitochondrial respiratory chain. ced-9 encodes a 280 amino acid protein showing sequence and structural similarities to the mammalian proto-oncogene bcl-2. Overexpression of bcl-2 can mimic the protective effect of ced-9 on C. elegans cell death and can prevent the ectopic cell deaths that occur in ced-9 loss-of-function mutants. These results suggest that ced-9 and bcl-2 are homologs and that the molecular mechanism of programmed cell death has been conserved from nematodes to mammals.
秀丽隐杆线虫基因ced-9的活性对于保护正常存活的细胞免于程序性细胞死亡是必需的。在此我们描述该基因的克隆及分子特征。ced-9是一个多顺反子位点的元件,该位点还包含基因cyt-1,其编码一种与线粒体呼吸链复合物II的细胞色素b560相似的蛋白质。ced-9编码一个280个氨基酸的蛋白质,该蛋白质在序列和结构上与哺乳动物原癌基因bcl-2相似。bcl-2的过表达可模拟ced-9对秀丽隐杆线虫细胞死亡的保护作用,并可防止在ced-9功能丧失突变体中发生的异位细胞死亡。这些结果表明ced-9和bcl-2是同源物,并且程序性细胞死亡的分子机制从线虫到哺乳动物是保守的。