Bifunctional killing activity encoded by conserved reaper proteins
Bifunctional killing activity encoded by conserved reaper proteins
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DOI：
10.1038/sj.cdd.4401406
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发表时间：
2004-07-01
影响因子：
12.4
通讯作者：
Abrams, JM
中科院分区：
文献类型：
--
作者：
Chen, P;Ho, SI;Abrams, JM
果蝇细胞凋亡激活剂映射到 Reaper 区域，部分是通过共享的 RHG 基序拮抗 IAP 蛋白来发挥作用。我们从绿头蝇 L. cuprina 中分离出 Reaper，它引发了果蝇细胞的广泛凋亡。在 GFP 融合的背景下测试了 Reaper 的保守区域，并鉴定出了与 RHG 不同的第二杀伤活性。称为 R3 的 20 个氨基酸肽赋予对焦点区室的靶向性并促进膜起泡。 R3 片段的杀伤与翻译抑制或 DIAP1 水平降低无关。同样，R3 诱导的细胞死亡仅通过 Dronc 沉默而受到适度抑制，并且与 DIAP1 没有可检测到的关联。相反，在 Reaper 的 C 末端发现了第二个与 R3 不同的 IAP 结合域，它与 DIAP1 结合，但未能触发细胞凋亡。总的来说，这些发现与 Reaper 杀伤细胞的单一效应器模型不一致，相反，表明 Reaper 编码通过不同效应器途径传播的保守双功能死亡活动。
Drosophila activators of apoptosis mapping to the Reaper region function, in part, by antagonizing IAP proteins through a shared RHG motif. We isolated Reaper from the Blowfly L. cuprina, which triggered extensive apoptosis in Drosophila cells. Conserved regions of Reaper were tested in the context of GFP fusions and a second killing activity, distinct from the RHG, was identified. A 20 amino-acid peptide, designated R3, conferred targeting to a focal compartment and promoted membrane blebbing. Killing by the R3 fragment did not correlate with translational suppression or with reduced DIAP1 levels. Likewise, R3-induced cell deaths were only modestly suppressed by silencing of Dronc and involved no detectable association with DIAP1. Instead, a second IAP-binding domain, distinct from the R3, was identified at the C terminus of Reaper that bound to DIAP1 but failed to trigger apoptosis. Collectively, these findings are inconsistent with single effector models for cell killing by Reaper and suggest, instead, that Reaper encodes conserved bifunctional death activities that propagate through distinct effector pathways.