Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis
Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis
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DOI：
10.1074/jbc.m300957200
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发表时间：
2003-06-20
影响因子：
4.8
通讯作者：
Wu, M
中科院分区：
文献类型：
--
作者：
Song, ZY;Yao, XB;Wu, M
Survivin是凋亡抑制蛋白（inhibitor of apoptosis protein，IAP）家族的一员，参与细胞凋亡抑制和细胞周期调控。然而，其抑制机制和亚细胞定位仍存在争议。在这份报告中，我们首次提供了证据，Survivin与Smac/DIABLO在体外和体内的物理相互作用。杆状病毒IAP重复基序中的点突变（D 71 R）和Survivin的C-末端缺失突变体（Surv-BIR）不能与Smac/DIABLO结合并消除其抑制凋亡的能力。成熟Smac/DIABLO的N端是形成Survivin.Smac复合物所必需的。Survivin和Smac/DIABLO的亚细胞分布表明，它们在间期共定位于细胞质内。此外，发现Survivin不能与caspase结合。我们还确定了Smac/DIABLO和XIAP的共同存在是Survivin在无细胞系统中抑制半胱天冬酶切割所必需的。总之，我们的研究结果提供了第一个证据，Smac/DIABLO和Survivin之间的相互作用是一个重要的步骤，抑制紫杉醇诱导的细胞凋亡。
Survivin is a member of the inhibitor of apoptosis protein (IAP) family that has been implicated in both apoptosis inhibition and cell cycle control. However, its inhibitory mechanism and subcellular localization remain controversial. In this report, we provided evidence for the first time that Survivin physically interacts with Smac/DIABLO both in vitro and in vivo. A point mutation (D71R) in the baculovirus IAP repeat motif and a C-terminal deletion mutant (Surv-BIR) of Survivin fail to bind to Smac/DIABLO and abrogate its ability to inhibit apoptosis. The N-terminal of mature Smac/DIABLO is absolutely required for Survivin.Smac complex formation. Subcellular distributions of Survivin and Smac/DIABLO showed that they co-localized within the cytosol during interphase. In addition, Survivin was found to be incapable of binding to caspase. We also identified that the co-presence of Smac/DIABLO and XIAP was required for Survivin to inhibit caspase cleavage in a cell-free system. In conclusion, our results provide the first evidence that the interaction between Smac/DIABLO and Survivin is an essential step underling the inhibition of apoptosis induced by Taxol.