High levels of dRYBP induce apoptosis in Drosophila imaginal cells through the activation of reaper and the requirement of trithorax, dredd and dFADD
High levels of dRYBP induce apoptosis in Drosophila imaginal cells through the activation of reaper and the requirement of trithorax, dredd and dFADD
复制标题
DOI：
10.1038/cr.2009.29
复制
发表时间：
2009-06-01
期刊：
影响因子：
44.1
通讯作者：
Busturia, Ana
中科院分区：
文献类型：
--
作者：
Gonzalez, Inma;Busturia, Ana
果蝇RYBP（dRYBP; Ring 1和YY 1结合蛋白）是一种多梳和三胸相互作用蛋白，其同源RYBP/DERYBP哺乳动物对应物表现出肿瘤细胞特异性杀伤活性。在这里，我们表明，虽然内源性dRYBP是不参与发育凋亡，高水平的外源性dRYBP诱导细胞凋亡的所有成虫盘的苍蝇，表明dRYBP凋亡活性是不是特定的肿瘤细胞。我们还表明，dRYBP诱导的细胞凋亡被高水平的p35或DIAP 1（果蝇凋亡抑制蛋白1）抑制，并需要促凋亡REAPER，HID和GRIM蛋白，顶端半胱天冬酶DREDD，衔接dFADD蛋白以及TRITHORAX（TRX），表观遗传转录调节因子的功能。此外，我们证明，过度表达TRX也诱导细胞凋亡的成虫盘。最后，我们表明，reaper-lacZ的表达上调后dRYBP诱导的细胞凋亡和TRX诱导的细胞凋亡的成虫盘和收割机基因是dRYBP在果蝇胚胎的直接目标。我们的研究结果表明，dRYBP触发受体介导的凋亡途径，也包括TRX依赖的基因表达的表观遗传调控。
Drosophila RYBP (dRYBP; Ring1 and YY1 Binding Protein) is a Polycomb and trithorax interacting protein, whose homologous RYBP/DEDAF mammalian counterparts exhibit tumor cell-specific killing activity. Here we show that although endogenous dRYBP is not involved in developmental apoptosis, high levels of exogenous dRYBP induce apoptosis in all the imaginal discs of the fly, indicating that dRYBP apoptotic activity is not specific to tumor cells. We also show that dRYBP-induced apoptosis is inhibited by high levels of either p35 or DIAP1 (Drosophila Inhibitor of Apoptosis Protein 1), and requires the function of the pro-apoptotic REAPER, HID and GRIM proteins, the apical caspase DREDD, the adaptor dFADD protein as well as TRITHORAX (TRX), an epigenetic transcriptional regulator. Furthermore, we demonstrate that overexpression of TRX also induces apoptosis in the imaginal discs. Finally, we show that the expression of reaper-lacZ is upregulated both upon dRYBP-induced apoptosis and upon TRX-induced apoptosis in imaginal discs and that the reaper gene is a direct target of dRYBP in Drosophila embryos. Our results indicate that dRYBP triggers in a receptor-mediated apoptotic pathway that also includes TRX-dependent epigenetic regulation of gene expression.