Neuralized functions as an E3 ubiquitin ligase during Drosophila development

The Notch pathway is a widely studied means of intercellular signaling resp onsible for the determination of cell fate, cell differentiation, and bound ary formation (reviewed in [1, 2]). The main effectors of this pathway, Not ch (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, althou gh its biochemical function is unknown. Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger dom ain 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 f or propagation and/or regulation of the signal.