ACTIVATION OF C-ELEGANS CELL-DEATH PROTEIN CED-9 BY AN AMINO-ACID SUBSTITUTION IN A DOMAIN CONSERVED IN BCL-2
ACTIVATION OF C-ELEGANS CELL-DEATH PROTEIN CED-9 BY AN AMINO-ACID SUBSTITUTION IN A DOMAIN CONSERVED IN BCL-2
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DOI：
10.1038/369318a0
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发表时间：
1994-05-26
期刊：
影响因子：
64.8
通讯作者：
HORVITZ, HR
中科院分区：
文献类型：
--
作者：
HENGARTNER, MO;HORVITZ, HR
秀丽隐杆线虫ced-9基因和人类原癌基因bcl-2都保护细胞免于程序性细胞死亡，是同一基因家族的成员（1-11）。ced-9和bcl-2是由于显性功能获得突变的影响而发现的（12-14）。这种bcl-2突变，这是常见于滤泡性淋巴瘤，是易位，导致正常Bcl-2蛋白在B细胞中的过度表达（1，13 -16）在这里，我们报告说，相比之下，ced-9（n1950）功能获得性突变影响ced-9的开放阅读框，并导致在所有ced-9/bcl-2中高度保守的区域中甘氨酸-谷氨酸取代。2家庭成员。我们的结论是，这种甘氨酸有一个重要的功能，在ced-9的调节，我们建议，改变这种甘氨酸在ced-9/bcl-2家族的其他成员可能会导致致癌激活。我们还提出了遗传证据，表明CED-9蛋白可能以两种不同的形式存在，对细胞死亡有相反的影响。
THE Caenorhabditis elegans gene ced-9 and the human protooncogene bcl-2 both of which protect cells from programmed cell death, are members of the same gene family(1-11). ced-9 and bcl-2 were discovered because of the effects of dominant gain-of-function mutations(12-14). Such bcl-2 mutations, which are commonly found in follicular lymphoma, are translocations that result in overexpression of a normal Bcl-2 protein in B cells(1,13-16) Here we report that, by contrast, the ced-9(n1950) gain-of-function mutation affects the open reading frame of ced-9 and results in a glycine-to-glutamate substitution in a region highly conserved among all ced-9/bcl-2 family members. We conclude that this glycine has an important function in ced-9 regulation, and we suggest that alteration of this glycine in other members of the ced-9/bcl-2 family might lead to oncogenic activation. We also present genetic evidence suggesting that the CED-9 protein might exist in two distinct forms that have opposite effects on cell death.