Lai E C, Deblandre G A, Kintner C, Rubin G M
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Dev Cell. 2001 Dec;1(6):783-94. doi: 10.1016/s1534-5807(01)00092-2.
The Drosophila gene neuralized (neur) has long been recognized to be essential for the proper execution of a wide variety of processes mediated by the Notch (N) pathway, but its role in the pathway has been elusive. In this report, we present genetic and biochemical evidence that Neur is a RING-type, E3 ubiquitin ligase. Next, we show that neur is required for proper internalization of Dl in the developing eye. Finally, we demonstrate that ectopic Neur targets Dl for internalization and degradation in a RING finger-dependent manner, and that the two exist in a physical complex. Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl.
果蝇基因“神经化”（neur）长期以来被认为对于由Notch（N）信号通路介导的多种过程的正常执行至关重要，但其在该信号通路中的作用一直难以捉摸。在本报告中，我们提供了遗传学和生物化学证据，表明Neur是一种RING型E3泛素连接酶。接下来，我们表明在发育中的眼睛中，neur对于Dl的正常内化是必需的。最后，我们证明异位表达的Neur以依赖于RING结构域的方式靶向Dl进行内化和降解，并且二者存在物理复合物中。总体而言，我们的数据表明Neur是一种泛素连接酶，通过促进Dl的内吞作用和降解来正向调节N信号通路。
