Target identification & developmental function of Greul1

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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.