Inhibitor of Apoptosis Proteins Physically Interact with and Block Apoptosis Induced by Drosophila Proteins HID and GRIM
Inhibitor of Apoptosis Proteins Physically Interact with and Block Apoptosis Induced by Drosophila Proteins HID and GRIM
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DOI：
10.1128/mcb.18.6.3300
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发表时间：
1998-06
影响因子：
5.3
通讯作者：
D. Vučić;W. Kaiser;Lois K. Miller
中科院分区：
文献类型：
--
作者：
D. Vučić;W. Kaiser;Lois K. Miller
Reaper （RPR）、HID和GRIM可激活果蝇发育过程中程序性死亡细胞的凋亡。我们之前的研究表明，鳞翅目SF-21细胞系中RPR的短暂过表达可诱导细胞凋亡，凋亡抑制剂（IAP）家族抗凋亡蛋白成员可抑制RPR诱导的细胞凋亡，并通过其BIR基序与RPR相互作用（D. Vucic， W. J. Kaiser， A. J. Harvey, and L. K. Miller, Proc. Natl）。学会科学。美国94:10183-10188,1997)。本研究发现，在SF-21细胞系中，短暂过表达HID和GRIM也可诱导细胞凋亡。杆状病毒和果蝇的IAPs阻断了HID-和grim诱导的细胞凋亡，并通过IAPs的BIR基序与它们发生物理相互作用。RPR、HID和GRIM共有的序列相似性区域，即每个蛋白的n端14个氨基酸，是HID诱导细胞凋亡及其与IAPs结合所必需的。当通过与不相关的非凋亡多肽融合而稳定过表达时，HID和GRIM的n端37个氨基酸足以诱导细胞凋亡并赋予IAP结合活性。然而，GRIM比HID更复杂，因为GRIM的c端124个氨基酸保留了诱导凋亡和IAP结合的活性，这表明在GRIM中存在两个独立的凋亡基序。IAPs与HID的共表达稳定了HID水平，并导致HID在点状核周位置积累，这与IAP定位一致。IAP与RPR、HID和GRIM的物理相互作用为IAP抑制这些果蝇促凋亡蛋白提供了一个共同的分子机制。
ABSTRACT Reaper (RPR), HID, and GRIM activate apoptosis in cells programmed to die during Drosophila development. We have previously shown that transient overexpression of RPR in the lepidopteran SF-21 cell line induces apoptosis and that members of the inhibitor of apoptosis (IAP) family of antiapoptotic proteins can inhibit RPR-induced apoptosis and physically interact with RPR through their BIR motifs (D. Vucic, W. J. Kaiser, A. J. Harvey, and L. K. Miller, Proc. Natl. Acad. Sci. USA 94:10183–10188, 1997). In this study, we found that transient overexpression of HID and GRIM also induced apoptosis in the SF-21 cell line. Baculovirus and Drosophila IAPs blocked HID- and GRIM-induced apoptosis and also physically interacted with them through the BIR motifs of the IAPs. The region of sequence similarity shared by RPR, HID, and GRIM, the N-terminal 14 amino acids of each protein, was required for the induction of apoptosis by HID and its binding to IAPs. When stably overexpressed by fusion to an unrelated, nonapoptotic polypeptide, the N-terminal 37 amino acids of HID and GRIM were sufficient to induce apoptosis and confer IAP binding activity. However, GRIM was more complex than HID since the C-terminal 124 amino acids of GRIM retained apoptosis-inducing and IAP binding activity, suggesting the presence of two independent apoptotic motifs within GRIM. Coexpression of IAPs with HID stabilized HID levels and resulted in the accumulation of HID in punctate perinuclear locations which coincided with IAP localization. The physical interaction of IAPs with RPR, HID, and GRIM provides a common molecular mechanism for IAP inhibition of theseDrosophila proapoptotic proteins.