Tait S W G, Werner A B, de Vries E, Borst J
Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Cell Death Differ. 2004 Aug;11(8):800-11. doi: 10.1038/sj.cdd.4401410.
Drosophila Reaper can bind inhibitor of apoptosis proteins (IAP) and thereby rescue caspases from proteasomal degradation. In insect cells, this is sufficient to induce apoptosis. Reaper can also induce apoptosis in mammalian cells, in which caspases need to be activated, usually via the mitochondrial pathway. Nevertheless, we find that Reaper efficiently induces apoptosis in mammalian cells in the absence of mitochondrial permeabilisation and cytochrome c release. Moreover, this capacity was only marginally affected by deletion of Reaper's amino-terminal IAP-binding motif. Independent of this motif, Reaper could globally suppress protein synthesis. Deletion of 20 amino acids from the carboxy-terminus of Reaper fully abrogated its potential to inhibit protein synthesis and to induce apoptosis in the absence of IAP-binding. Our findings indicate that the newly identified capacity of Reaper to suppress protein translation can operate in mammalian cells and may be key to its pro-apoptotic activity.
果蝇促凋亡蛋白（Reaper）能够结合凋亡抑制蛋白（IAP），从而使半胱天冬酶免受蛋白酶体降解。在昆虫细胞中，这足以诱导细胞凋亡。Reaper也能在哺乳动物细胞中诱导细胞凋亡，在哺乳动物细胞中，半胱天冬酶通常需要通过线粒体途径被激活。然而，我们发现Reaper在不存在线粒体通透性改变和细胞色素c释放的情况下，也能有效地在哺乳动物细胞中诱导细胞凋亡。此外，Reaper的氨基末端IAP结合基序缺失对其诱导细胞凋亡的能力影响甚微。不依赖于该基序，Reaper能够全面抑制蛋白质合成。从Reaper的羧基末端缺失20个氨基酸完全消除了其在缺乏IAP结合时抑制蛋白质合成和诱导细胞凋亡的潜力。我们的研究结果表明，新发现的Reaper抑制蛋白质翻译的能力在哺乳动物细胞中起作用，并且可能是其促凋亡活性的关键。
