Royet J, Bouwmeester T, Cohen S M
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
EMBO J. 1998 Dec 15;17(24):7351-60. doi: 10.1093/emboj/17.24.7351.
Signaling by Notch family receptors is involved in many cell-fate decisions during development. Several modifiers of Notch activity have been identified, suggesting that regulation of Notch signaling is complex. In a genetic screen for modifiers of Notch activity, we identified a gene encoding a novel WD40-repeat protein. The gene is called Notchless, because loss-of-function mutant alleles dominantly suppress the wing notching caused by certain Notch alleles. Reducing Notchless activity increases Notch activity. Overexpression of Notchless in Xenopus or Drosophila appears to have a dominant-negative effect in that it also increases Notch activity. Biochemical studies show that Notchless binds to the cytoplasmic domain of Notch, suggesting that it serves as a direct regulator of Notch signaling activity.
Notch家族受体介导的信号传导参与了发育过程中许多细胞命运的决定。已鉴定出几种Notch活性的调节因子，这表明Notch信号传导的调控很复杂。在一项针对Notch活性调节因子的遗传筛选中，我们鉴定出一个编码新型WD40重复蛋白的基因。该基因被称为Notchless，因为功能丧失的突变等位基因可显性抑制某些Notch等位基因引起的翅缺刻。降低Notchless的活性会增加Notch的活性。在非洲爪蟾或果蝇中过表达Notchless似乎具有显性负效应，因为它也会增加Notch的活性。生化研究表明，Notchless与Notch的细胞质结构域结合，这表明它作为Notch信号传导活性的直接调节因子发挥作用。
