Notchless encodes a novel WD40-repeat-containing protein that modulates Notch signaling activity
Notchless encodes a novel WD40-repeat-containing protein that modulates Notch signaling activity
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DOI：
10.1093/emboj/17.24.7351
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发表时间：
1998-12-15
期刊：
影响因子：
11.4
通讯作者：
Cohen, SM
中科院分区：
文献类型：
--
作者：
Royet, J;Bouwmeester, T;Cohen, SM
Notch家族受体的信号传导参与发育过程中的许多细胞命运决定。已经鉴定了Notch活性的几种修饰剂，表明Notch信号传导的调节是复杂的。在对Notch活性的修饰剂的遗传筛选中，我们鉴定了编码新的WD 40重复蛋白的基因，该基因被称为Notchless，因为功能丧失突变等位基因主要抑制由某些Notch等位基因引起的翅切口，降低Notchless活性增加Notch活性。Notchless在爪蟾或果蝇中的过表达似乎具有显性负效应，因为它也增加Notch活性。生物化学研究表明，Notchless与Notch的胞质结构域结合，表明它是Notch信号传导活性的直接调节剂。
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.