González Inma, Busturia Ana
Centro de Biología Molecular Severo Ochoa CSIC-UAM, c) Nicolás Cabrera 1, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
Cell Res. 2009 Jun;19(6):747-57. doi: 10.1038/cr.2009.29.
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.
果蝇RYBP（dRYBP；Ring1和YY1结合蛋白）是一种与多梳蛋白和三胸蛋白相互作用的蛋白，其同源的哺乳动物RYBP/DEDAF具有肿瘤细胞特异性杀伤活性。我们在此表明，尽管内源性dRYBP不参与发育性凋亡，但高水平的外源性dRYBP会在果蝇的所有成虫盘诱导凋亡，这表明dRYBP的凋亡活性并非肿瘤细胞特有的。我们还表明，高水平的p35或DIAP1（果蝇凋亡抑制蛋白1）可抑制dRYBP诱导的凋亡，且该过程需要促凋亡蛋白REAPER、HID和GRIM、顶端半胱天冬酶DREDD、衔接蛋白dFADD以及表观遗传转录调节因子三胸蛋白（TRX）的功能。此外，我们证明TRX的过表达也会在成虫盘中诱导凋亡。最后，我们表明在成虫盘中，dRYBP诱导的凋亡和TRX诱导的凋亡都会使reaper-lacZ的表达上调，并且在果蝇胚胎中，reaper基因是dRYBP的直接靶标。我们的结果表明，dRYBP在一种受体介导的凋亡途径中发挥作用，该途径还包括TRX依赖的基因表达表观遗传调控。
