Archipelago (Ago) is a Drosophila homolog of mammalian F-box and WD repeat domain-containing 7 (FBW7, also known as FBXW7). In previous studies, FBW7 has been addressed as a tumor suppressor mediating ubiquitin-dependent proteolysis of several oncogenic proteins. Ubiquitination is a type of protein modification that directs protein for degradation as well as sorting. The level of beta-catenin (β-cat), an intracellular signal transducer in Wnt signaling pathway, is reduced upon overexpression of FBW7 in human cancer cell lines. Loss of function mutations in FBW7 and overactive Wnt signaling have been reported to be responsible for human cancers. We found that Ago is important for the formation of shafts in chemosensory bristles at wing margin. This loss of shaft phenotype by knockdown of ago was rescued by knockdown of wingless (wg) whereas wing notching phenotype by knockdown of wg was rescued by knockdown of ago, establishing an antagonistic relationship between ago and wg. In line with this finding, knockdown of ago increased the level of Armadillo (Arm), a homolog of β-cat, in Drosophila tissue. Furthermore, knockdown of ago increased the level of Distal-less (Dll) and extracellular Wg in wing discs. In S2 cells, the amount of secreted Wg was increased by knockdown of Ago but decreased by Ago overexpression. Therefore, Ago plays a previously unidentified role in the inhibition of Wg secretion. Ago-overexpressing clones in wing discs exhibited accumulation of Wg in endoplasmic reticulum (ER), suggesting that Ago prevents Wg protein from moving to Golgi from ER. We concluded that Ago plays dual roles in inhibiting Wg signaling. First, Ago decreases the level of Arm, by which Wg signaling is downregulated in Wg-responding cells. Second, Ago decreases the level of extracellular Wg by inhibiting movement of Wg from ER to Golgi in Wg-producing cells.

中文翻译：

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Wingless和群岛，一种E3泛素连接酶和人类肿瘤抑制因子FBW7的同源物，在机翼发育中表现出拮抗关系。

群岛（Ago）是果蝇的哺乳动物F-box和WD重复域含7（FBW7，也称为FBXW7）的同源物。在先前的研究中，FBW7被认为是介导多种致癌蛋白的泛素依赖性蛋白水解的肿瘤抑制剂。泛素化是蛋白质修饰的一种类型，可指导蛋白质降解和分类。当人癌细胞系中FBW7过表达时，β-连环蛋白（β-cat）（Wnt信号通路中的细胞内信号转导子）的水平会降低。据报道，FBW7功能丧失和Wnt信号过度活跃是造成人类癌症的原因。我们发现，Ago对于机翼边缘化学感应硬毛中杆的形成很重要。通过无翅（wg）的敲除挽救了轴击表型的这种丧失，而通过无翅（wg）的击倒挽救了通过wg的击倒的翼状缺口表型，从而在ago与wg之间建立了对抗关系。根据这一发现，以前的基因敲除增加了果蝇组织中β-cat同源物Armadillo（Arm）的水平。此外，以前的组合降低了翼盘中的远距（Dll）和细胞外Wg的水平。在S2细胞中，分泌的Wg的量通过Ago的敲低而增加，但通过Ago的过表达而减少。因此，Ago在抑制Wg分泌中起着以前未曾认识的作用。翼盘中过表达Ago的克隆在内质网（ER）中显示出Wg的积累，这表明Ago阻止了Wg蛋白从ER转移到高尔基体。我们得出的结论是，Ago在抑制Wg信号传导中起双重作用。首先，Ago降低了Arm的水平，从而降低了Wg响应细胞中的Wg信号。其次，Ago通过抑制Wg产生细胞中Wg从ER向高尔基体的移动来降低细胞外Wg的水平。