Evans E K, Kuwana T, Strum S L, Smith J J, Newmeyer D D, Kornbluth S
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3686, C366 LSRC, Research Drive, Durham, NC 27710, USA.
EMBO J. 1997 Dec 15;16(24):7372-81. doi: 10.1093/emboj/16.24.7372.
The reaper protein of Drosophila melanogaster has been shown to be a central regulator of apoptosis in that organism. However, it has not been shown to function in any vertebrate nor have the cellular components required for its action been defined. In this report we show that reaper can induce rapid apoptosis in vitro using an apoptotic reconstitution system derived from Xenopus eggs. Moreover, we show that a subcellular fraction enriched in mitochondria is required for this process and that reaper, acting in conjunction with cytosolic factors, can trigger mitochondrial cytochrome c release. Bcl-2 antagonizes these effects, but high levels of reaper can overcome the Bcl-2 block. These results demonstrate that reaper can function in a vertebrate context, suggesting that reaper-responsive factors are conserved elements of the apoptotic program.
黑腹果蝇的收割者蛋白已被证明是该生物体中细胞凋亡的核心调节因子。然而，它尚未在任何脊椎动物中发挥作用，其作用所需的细胞成分也未明确。在本报告中，我们表明收割者可以利用源自非洲爪蟾卵的凋亡重建系统在体外诱导快速细胞凋亡。此外，我们表明该过程需要富含线粒体的亚细胞组分，并且收割者与胞质因子协同作用可触发线粒体细胞色素c的释放。Bcl-2可拮抗这些作用，但高水平的收割者可克服Bcl-2的阻断作用。这些结果表明收割者可在脊椎动物环境中发挥作用，这表明对收割者有反应的因子是凋亡程序中的保守元件。
