NOPO modulates Egr-induced JNK-independent cell death in Drosophila
NOPO modulates Egr-induced JNK-independent cell death in Drosophila
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NOPO 调节果蝇中 Egr 诱导的 JNK 独立细胞死亡
DOI：
10.1038/cr.2011.135
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发表时间：
2012-02-01
期刊：
影响因子：
44.1
通讯作者：
Xue, Lei
中科院分区：
文献类型：
--
作者：
Ma, Xianjue;Huang, Jiuhong;Xue, Lei
肿瘤坏死因子（TNF）家族配体在调节包括增殖、分化和存活在内的多种细胞过程中发挥重要作用。果蝇TNF直系同源物Eiger（Egr）的表达诱导JNK依赖性细胞死亡，而半胱天冬酶在这一过程中的作用仍然难以捉摸。为了进一步描述Egr触发的细胞死亡途径，我们进行了遗传筛选，以确定Egr诱导的细胞死亡表型的显性修饰剂。在这里，我们报告说，Egr eliminates一个半胱天冬酶介导的细胞死亡途径独立的JNK信号。此外，我们显示NOPO，果蝇的直系同源物TRIP（TRAF相互作用蛋白）编码E3泛素连接酶，调节Egr诱导的半胱天冬酶介导的细胞死亡，通过转录激活促凋亡基因收割机和隐藏。最后，我们发现Bendless和dUEV 1a，一种泛素结合的E2酶复合物，调节NOPO触发的细胞死亡。我们的研究结果表明，Ben-dUEV 1a复合物构成了一个分子开关，将Egr诱导的细胞死亡信号分为两条途径，分别由JNK和caspase介导。
Tumor necrosis factor (TNF) family ligands play essential roles in regulating a variety of cellular processes including proliferation, differentiation and survival. Expression of Drosophila TNF ortholog Eiger (Egr) induces JNK-dependent cell death, while the roles of caspases in this process remain elusive. To further delineate the Egr-triggered cell death pathway, we performed a genetic screen to identify dominant modifiers of the Egr-induced cell death phenotype. Here we report that Egr elicits a caspase-mediated cell death pathway independent of JNK signaling. Furthermore, we show NOPO, the Drosophila ortholog of TRIP (TRAF interacting protein) encoding an E3 ubiquitin ligase, modulates Egr-induced Caspase-mediated cell death through transcriptional activation of pro-apoptotic genes reaper and hid. Finally, we found Bendless and dUEV1a, an ubiquitin-conjugating E2 enzyme complex, regulates NOPO-triggered cell death. Our results indicate that the Ben-dUEV1a complex constitutes a molecular switch that bifurcates the Egr-induced cell death signaling into two pathways mediated by JNK and caspases respectively.