Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death
Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death
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DOI：
10.1073/pnas.97.2.662
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发表时间：
2000-01-18
影响因子：
11.1
通讯作者：
Miura, M
中科院分区：
文献类型：
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作者：
Igaki, T;Kanuka, H;Miura, M
Bcl-2/CED-9 蛋白家族包括抗凋亡和促凋亡成员，在程序性细胞死亡中发挥关键调节作用。我们在此报告了 Drob-1 的鉴定和表征，Drob-1 是 Bcl-2/CED-9 家族中第一个被分离的果蝇成员。 Drob-1 包含四个保守的 Bcl-2 同源结构域（BH1、BH2、BH3 和 BH4）和一个 C 端疏水结构域。 Drob-1 在发育中的果蝇眼睛中的异位表达导致了粗糙的眼睛表型。此外，当在果蝇 S2 细胞中过度表达时，Drob-1 会诱导细胞凋亡并伴随 caspase 活性升高。然而，这种 Drob-1 诱导的细胞死亡不能被杆状病毒 p35（一种广谱 caspase 抑制剂）拮抗。 Drob-1 定位于胞质内膜，主要定位于线粒体膜，缺乏疏水性 C 末端的突变体 Drob-1 失去了其线粒体定位和促凋亡活性。这些结果表明，Drob-1 通过在线粒体诱导 caspase 依赖性和非依赖性途径来促进细胞死亡。我们对 Drob-1 的鉴定和进一步的遗传分析应该可以加深对 Bcl-2/CED-9 家族成员和其他相关蛋白调节细胞凋亡的普遍机制的了解。
The Bcl-2/CED-9 family of proteins, which includes both antiapoptotic and proapoptotic members, plays key regulating roles in programmed cell death. We report here the identification and characterization of Drob-1, the first Drosophila member of the Bcl-2/CED-9 family to be isolated. Drob-1 contains four conserved Bcl-2 homology domains (BH1, BH2. BH3, and BH4) and a C-terminal hydrophobic domain. Ectopic expression of Drob-1 in the developing Drosophila eye resulted in a rough-eye phenotype. Furthermore, when overexpressed in Drosophila S2 cells, Drob-1 induced apoptosis accompanied by elevated caspase activity. This Drob-1-induced cell death, however, could not be antagonized by baculovirus p35, a broad-spectrum caspase inhibitor. Drob-1 was localized to the intracytoplasmic membranes, predominantly to the mitochondrial membranes, and a mutant Drob-1 lacking the hydrophobic C terminus lost both its mitochondrial localization and its proapoptotic activity. These results suggest that Drob-1 promotes cell death by inducing both caspase-dependent and -independent pathways at the mitochondria. Our identification of Drob-1 and further genetic analysis should provide increased understanding of the universal mechanisms by which the Bcl-2/CED-9 family members and other related proteins regulate apoptosis.