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首页> 外文期刊>Development >The Bax/Bak ortholog in Drosophila, Debcl, exerts limited control over programmed cell death.
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The Bax/Bak ortholog in Drosophila, Debcl, exerts limited control over programmed cell death.

机译:果蝇Debcl中的Bax / Bak直系同源物对程序性细胞死亡的控制有限。

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摘要

Bcl-2 family members are pivotal regulators of programmed cell death (PCD). In mammals, pro-apoptotic Bcl-2 family members initiate early apoptotic signals by causing the release of cytochrome c from the mitochondria, a step necessary for the initiation of the caspase cascade. Worms and flies do not show a requirement for cytochrome c during apoptosis, but both model systems express pro- and anti-apoptotic Bcl-2 family members. Drosophila encodes two Bcl-2 family members, Debcl (pro-apoptotic) and Buffy (anti-apoptotic). To understand the role of Debcl in Drosophila apoptosis, we produced authentic null alleles at this locus. Although gross development and lifespans were unaffected, we found that Debcl was required for pruning cells in the developing central nervous system. debcl genetically interacted with the ced-4/Apaf1 counterpart dark, but was not required for killing by RHG (Reaper, Hid, Grim) proteins. We found that debcl(KO) mutants were unaffected for mitochondrial density or volume but, surprisingly, in a model of caspase-independent cell death, heterologous killing by murine Bax required debcl to exert its pro-apoptotic activity. Therefore, although debcl functions as a limited effector of PCD during normal Drosophila development, it can be effectively recruited for killing by mammalian members of the Bcl-2 gene family.
机译:Bcl-2家族成员是程序性细胞死亡(PCD)的关键调节剂。在哺乳动物中,促凋亡的Bcl-2家族成员通过引起线粒体中细胞色素c的释放来启动早期凋亡信号,这是启动caspase级联反应所必需的步骤。蠕虫和苍蝇在细胞凋亡过程中并未显示出对细胞色素c的需求,但两种模型系统均表达促凋亡和抗凋亡Bcl-2家族成员。果蝇编码两个Bcl-2家族成员,Debcl(促凋亡)和Buffy(抗凋亡)。为了了解Debcl在果蝇细胞凋亡中的作用,我们在该基因座处产生了真实的无效等位基因。尽管总体发育和寿命没有受到影响,但我们发现在发育中的中枢神经系统中修剪细胞需要Debcl。 debcl与ced-4 / Apaf1对应物Dark发生了遗传相互作用,但RHG(Reaper,Hid,Grim)蛋白杀伤并不是必需的。我们发现,debcl(KO)突变体不影响线粒体的密度或体积,但令人惊讶的是,在不依赖caspase的细胞死亡模型中,鼠Bax的异源杀伤需要debcl发挥其促凋亡活性。因此,尽管debcl在果蝇正常发育过程中起着有限的PCD效应子的作用,但它可以被Bcl-2基因家族的哺乳动物有效地募集杀死。

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