Neuralized functions as an E3 ubiquitin ligase during Drosophila development (original) (raw)

The Notch pathway is a widely studied means of to the protein target via the E3 ubiquitin ligase. The E3 ubiquitin ligases are responsible for conferring target or intercellular signaling responsible for the determination of cell fate, cell differentiation, and substrate specificity. boundary formation (reviewed in [1, 2]). The main effectors of this pathway, Notch (N) and Delta (Dl), Several recent studies have implicated ubiquitination as have been shown to function as a receptor and a potential regulatory mechanism involved in N signaling. ligand, respectively. Genetic and phenotypic studies The molecular characterization of Suppressor of deltex, Su suggest that Neuralized (Neu), a RING finger (dx), which has been shown to genetically interact with protein, also plays a role within the N-Dl pathway, N, revealed that it encodes a HECT domain found in although its biochemical function is unknown. proteins that possess E3 ubiquitin ligase activity [6]. Al-Here, we show that Neu is required at the plasma though a direct role for Su (dx) in the ubiquitination of membrane for functional activity and that its RING Notch (N) has not yet been shown, a related mammalian finger domain acts as an E3 ubiquitin ligase. These protein called Itch has been shown to interact with and data suggest that the role of Neu is to target ubiquitinate N in vitro and in human Jurkat cells [7]. components of the N-Dl pathway for ubiquitination, Further genetic evidence implicating ubiquitination in N allowing for propagation and/or regulation of the signaling comes from observations that mutations in the signal. ␤2 and ␤6 subunits of the 20S proteasome cause N gainof-function phenotypes during sense organ development Addresses: *Program in Developmental Biology, † Program in Cell in Drosophila [8]. These mutations also increase the stabil-Biology,

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