Target identification & developmental function of Greul1

描述（由申请人提供）：调节发育过程的信号通路已经进化出一系列机制来确保其精确调控。其中一个关键机制是泛素化，它涉及到几个关键发育途径中关键信号分子的破坏，包括Wnt和Hedgehog。我们发现了一种新的E3泛素连接酶GREUL1，它在非洲爪蟾胚胎中具有独特的发育表型。虽然GREUL1可以从表皮生成异位神经元组织，但它也可以抑制中胚层内血管的形成。这种双功能作用是不寻常的，可能是由于不同组织中发现的GREUL1泛素靶点的差异。因此，了解GREUL1功能的关键是确定其特定的靶底物。在这里，我们提出了一种筛选E3连接酶靶标的方法，并将使用这种方法寻找GREUL1的底物。此外，我们旨在了解哺乳动物GREUL1在神经和血管发育中的功能。这些方法对我们理解GREUL1调节的信号通路至关重要，并将使我们深入了解GRUEL1的机制和发育功能。

DESCRIPTION (provided by applicant): Signaling pathways that regulate developmental processes have evolved a host of mechanisms to ensure their precise regulation. One critical mechanism is ubquitination, which has been implicated in the destruction of key signaling molecules in several critical developmental pathways, including Wnt and Hedgehog. We have identified a new E3 ubiquitin ligase, GREUL1, which has a unique developmental phenotype in Xenopus embryos. While GREUL1 can generate ectopic neuronal tissue from epidermis, it can also repress the formation of blood and vessels within the mesoderm. This bi-functional effect is unusual, and may be due to differences in GREUL1 ubiquitin targets found in the different sets of tissues. Therefore, a key to understanding the function of GREUL1 is to identify its specific target substrates. Here we present a method to screen for targets of E3 ligases and will use this approach to find substrates for GREUL1. Furthermore, we aim to understand the function of mammalian GREUL1 during neural and vascular development. These approaches are essential to our understanding of the signaling pathways that GREUL1 regulates and will give us an insight into the function of GRUEL1 mechanistically and developmentally.