Deblandre G A, Lai E C, Kintner C
The Salk Institute for Biological Studies, P.O. Box 85800, La Jolla, CA 92186, USA.
Dev Cell. 2001 Dec;1(6):795-806. doi: 10.1016/s1534-5807(01)00091-0.
Notch signaling in Drosophila requires a RING finger (RF) protein encoded by neuralized. Here we show that the Xenopus homolog of neuralized (Xneur) is expressed where Notch signaling controls cell fate choices in early embryos. Overexpressing XNeur or putative dominant-negative forms in embryos inhibits Notch signaling. As expected for a RF protein, we show that XNeur fulfills the biochemical requirements of ubiquitin ligases. We also show that wild-type XNeur decreases the cell surface level of the Notch ligand, XDelta1, while putative inhibitory forms of XNeur increase it. Finally, we provide evidence that XNeur acts as a ubiquitin ligase for XDelta1 in vitro. We propose that XNeur plays a conserved role in Notch activation by regulating the cell surface levels of the Delta ligands, perhaps directly, via ubiquitination.
果蝇中的Notch信号传导需要由neuralized编码的一种环状结构域（RF）蛋白。我们在此表明，neuralized的非洲爪蟾同源物（Xneur）在Notch信号传导控制早期胚胎细胞命运选择的部位表达。在胚胎中过表达XNeur或推定的显性负性形式会抑制Notch信号传导。正如对一种RF蛋白的预期，我们表明XNeur满足泛素连接酶的生化要求。我们还表明，野生型XNeur降低了Notch配体XDelta1的细胞表面水平，而XNeur的推定抑制形式则使其增加。最后，我们提供证据表明XNeur在体外作为XDelta1的泛素连接酶发挥作用。我们提出，XNeur可能通过泛素化直接调节Delta配体的细胞表面水平，从而在Notch激活中发挥保守作用。
