GENETIC-CONTROL OF PROGRAMMED CELL-DEATH IN DROSOPHILA

GENETIC-CONTROL OF PROGRAMMED CELL-DEATH IN DROSOPHILA
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DOI:
10.1126/science.8171319
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发表时间:
1994-04-29
期刊:
影响因子:
56.9
通讯作者:
STELLER, H
STELLER, H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
WHITE, K;GRETHER, ME;STELLER, H

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一个基因,收割机(rpr),似乎发挥了中央控制功能的程序性细胞死亡(凋亡)的启动在果蝇被确定。事实上,果蝇胚胎发育过程中通常发生的所有程序性细胞死亡,在包含reaper基因的小缺失纯合子胚胎中都被阻断。变异胚胎含有许多额外的细胞,无法孵化,但许多其他方面的发展似乎很正常。包括reaper基因在内的基因缺失也能保护胚胎免受x射线照射和发育缺陷引起的细胞凋亡。然而,高剂量的X射线诱导了突变胚胎的一些凋亡,并且产生的尸体被巨噬细胞吞噬。这些数据表明,基本的细胞死亡程序是完整的,虽然它没有被激活的突变胚胎。克隆了缺失所包含的DNA,并根据克隆的DNA在种系转化实验中恢复细胞死亡缺陷胚胎的细胞凋亡的能力鉴定了reaper基因。reaper基因似乎编码一种与已知蛋白质没有同源性的小肽,并且reaper信使RNA在注定要经历凋亡的细胞中表达。
A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. Mutant embryos contained many extra cells and failed to hatch, but many other aspects of development appeared quite normal. Deletions that include reaper also protected embryos from apoptosis caused by x-irradiation and developmental defects. However, high doses of x-rays induced some apoptosis in mutant embryos, and the resulting corpses were phagocytosed by macrophages. These data suggest that the basic cell death program is intact although it was not activated in mutant embryos. The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis.