Notch信号通路在昆虫翅发育过程中起重要的调控作用，其信号转导的关键步骤是Notch受体被激活后通过酶解产生具有转录调控活性的Notch胞内结构域蛋白（Notch intracellular domain，NICD）。我们实验室前期通过遗传筛选鉴定出了两个泛素化相关因子作用于NICD蛋白从而调控Notch通路活性，暗示泛素化修饰是NICD蛋白活性调控的重要手段。为了验证这一假说，本项目将以模式昆虫黑腹果蝇为材料，集中研究昆虫翅发育过程中: 1.泛素连接酶ago对NICD蛋白泛素化及活性调控机制；2.去泛素酶eIF3h对对NICD蛋白泛素化及活性调控机制；3.NICD泛素化状态对其活性及稳态的调控机理。通过上述研究，希望能初步揭示昆虫翅发育过程中NICD蛋白泛素化对其稳态调控的重要性，填补NICD蛋白活性调控机制研究的空白，加深对Notch信号通路调控机制的理解。

The Notch signaling pathway is crucial for insect wing development. In the signal receiving cells, the Notch receptor is cleaved to generate Notch intracellular domain (NICD), and NICD translocates into the nucleus to activate downstream targets. Through genetic screenings, we have identified two ubiquitination related regulators that function on the NICD protein. We hypothesize that ubiquitination plays important role in NICD activity control. Using the model insect Drosophila melanogaster, we propose to investigate: 1. the molecular mechanisms of how ubiquitin ligase ago regulates NICD ubiquitination and signal activity; 2. how deubiquitinase eIF3h regulates NICD ubiquitination and signal activity; 3. how ubiquitination affects NICD protein homeostasis. Our proposed studies will help to reveal the integrated network of NICD homeostasis regulation during insect wing development.