Neuralized functions as an E3 ubiquitin ligase during Drosophila development

The Notch pathway is a widely studied means of intercellular signaling responsible for the determination of cell fate, cell differentiation, and boundary formation (reviewed in [1, 2]). The main effectors of this pathway, Notch (N) and Delta (DI), have been shown to function as a receptor and ligand, respectively. Genetic and phenotypic studies suggest that Neuralized (Neu), a RING finger protein, also plays a role within the N-DI pathway, although its biochemical function is unknown. Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. These data suggest that the role of Neu is to target components of the N-DI pathway for ubiquitination, allowing for propagation and/or regulation of the signal.