Doom, a product of the Drosophila mod(mdg4) gene, induces apoptosis and binds to baculovirus inhibitor-of-apoptosis proteins
Doom, a product of the Drosophila mod(mdg4) gene, induces apoptosis and binds to baculovirus inhibitor-of-apoptosis proteins
复制标题
DOI：
10.1128/mcb.17.5.2835
复制
发表时间：
1997-05-01
影响因子：
5.3
通讯作者：
Miller, LK
中科院分区：
文献类型：
--
作者：
Harvey, AJ;Bidwai, AP;Miller, LK
杆状病毒凋亡相关基因家族存在于哺乳动物、昆虫和杆状病毒中，但其阻断细胞凋亡的机制尚不清楚。我们已经鉴定了果蝇mod（mdg 4）基因编码的与杆状病毒IAP结合的蛋白。这种蛋白质在昆虫细胞中诱导快速凋亡，因此我们将其命名为Doom。杆状病毒IAP和P35（一种天冬氨酸特异性半胱氨酸蛋白酶抑制剂）阻断了Doom诱导的细胞凋亡。doom cDNA的3'外显子编码的羧基端负责诱导凋亡和IAP的结合，这使其与其他mod（mdg 4）cDNA不同。Doom定位于细胞核，而IAPs定位于细胞质，但当一起表达时，Doom和IAPs都定位于细胞核。因此，IAP可能通过与细胞凋亡途径中的Doom样蛋白相互作用并改变其行为来阻断细胞凋亡。
A family of baculovirus inhibitor-of-apoptosis (IAP) genes is present in mammals, insects, and baculoviruses, but the mechanism by which they block apoptosis is unknown. We have identified a protein encoded by the Drosophila mod(mdg4) gene which bound to the baculovirus IAPs. This protein induced rapid apoptosis in insect cells, and consequently we have named it Doom. Baculovirus IAPs and P35, an inhibitor of aspartate-specific cysteine proteases, blocked Doom-induced apoptosis. The carboxyl terminus encoded by the 3' exon of the doom cDNA, which distinguishes it from other mod(mdg4) cDNAs, was responsible for induction of apoptosis and engagement of the IAPs. Doom localized to the nucleus, while the IAPs localized to the cytoplasm, but when expressed together, Doom and the IAPs both localized in the nucleus. Thus, IAPs might block apoptosis by interacting with and modifying the behavior of Doom-like proteins that reside in cellular apoptotic pathways.