PDF(Pubmed)
Abstract：
The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.
摘要：
Notch通路是一种进化上保守的信号系统，在多个水平上受到复杂的调节，并影响发育的不同方面。为了鉴定参与Notch信号及其调节的新成分，我们进行了蛋白质相互作用筛选，将非肌肉肌球蛋白II拉链（Zip）鉴定为Notch的相互作用伴侣。通过免疫共沉淀研究进一步验证了Notch和Zip之间的物理相互作用。免疫细胞化学分析显示Notch和Zip共定位在相同的细胞质区室中。zip的不同等位基因也显示出与Notch途径组分的强遗传相互作用。Zip的下调导致机翼表型，让人想起Notch功能丧失表型和Notch下游靶标的扰动表达，切和死人。Further,Notch和Zip之间的协同相互作用导致这些Notch靶标的高度异位表达。Zip的过表达增强了激活的Notch诱导的幼虫组织肿瘤表型。Notch-Zip协同作用导致JNK途径的活化,从而导致MMP活化和增殖。一起来看,我们的研究结果表明，Zip可能在Notch信号的调节中起重要作用。
